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[Expression of squamous cell carcinoma-associated antigen in bladder cancer cells--a comparative study with the expression of proliferating cell nuclear antigen (PCNA)].

We investigated the expression of squamous cell carcinoma-associated antigen (SCC-Ag) and proliferating cell nuclear antigen (PCNA) in bladder carcinoma cells using immunohistochemical techniques. Tissues with 10% or more cells stained for SCC-Ag were defined as positive for the antigen. All grade 1-transitional cell carcinomas (TCCs) and 87% of grade 2-TCCs were negative for cytoplasmic SCC-Ag. However, 57.6% of grade 3-TCCs not associated with squamous metaplasia and 80% of those associated with squamous metaplasia showed strongly positive cytoplasmic SCC-Ag. Of squamous cell carcinomas, the well or moderately differentiated carcinomas showed a higher incidence (80-100%) of the antigen in the cytoplasm than the poorly differentiated ones (25%). Nuclear SCC-Ag was found in 63.6% of grade 1-TCCs, 46.3% of grade 2-TCCs and 54.9% of grade 3-TCCs not associated with squamous metaplasia. However, grade 3-TCCs with squamous metaplasia and squamous cell carcinomas were negative for nuclear SCC-Ag. The positive rate for PCNA increased from grade 1 to grade 2, grade 3 without squamous metaplasia and grade 3 with squamous metaplasia in the TCCs. All squamous cell carcinomas showed a high positive rate, irrespective of the differentiation. Multiple regression analysis revealed a closer association between the expression of cytoplasmic SCC-Ag and the histological grade of TCCs.

Antigens, Neoplasm↗

[Clinical analysis of patients operated with squamous cell carcinoma of the uterine cervix].

OBJECTIVES: The aim of our study was clinical analysis of patients operated with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Between 1972 and 1991 at the 2nd Department of Obstetrics and Gynecology Medical University of Gdańsk 687 total hysterectomies in Wertheim-Meigs method were performed in the patients with, various clinical stages cervical carcinoma. The clinical analysis has been done in 499 patients with diagnosed invasive cervical cancer stages Ia2, Ib and IIa. The clinical progression of cancer was established on the basis of FIGO classification from the year 1985. In the 18 patients invasive cervical cancer occurred together with a pregnancy (cervical cancer was diagnosed in the I, II and III trimester). In this group squamous carcinoma was diagnosed in 16 cases (88.8%). Endocervical type was diagnosed in 8 cases (1.6%), among which 4 cases were of a squamous type (0.8%). Two 10-year-periods of time have been separated: since 01.01.1972 to 31.12.1981 and since 01.01.1982 to 31.12.1991. RESULTS AND CONCLUSIONS: In the studied 20-year period (1972-1991) in all 499 performed operations squamous carcinoma was the most often occurring histological type of cervical cancer--439 cases (88.0). Comparing the incidence of squamous carcinoma in both 10-year periods of time there were no significant differences (only almost a 3-fold decrease of the incidence of microcellular cancer in the second decade was observed). It was stated that a percentage share of squamous carcinoma in the clinical stages Ib and IIa did not change. The number of pregnancies and labours in the patients with squamous carcinoma was close to the patients with other histological types of cervical cancer. The mean age of patients with squamous carcinoma was 45.6 (22-74) and was lower than the age of patients with adenocarcinoma--49.1 years (22-73). The clinical symptoms of a cancer occurred in 81.4% of the studied group. Asymptomatic course was seen in 18.6% of patients. The incidence of positive lymph nodes in the patients with squamous carcinoma stages Ib-IIa was close to the patients with carcinoma adenosquamous (25.0% and 23.7% respectively) and lower than in the case of adenocarcinoma (34%) or anaplastic carcinoma (33.3%, because of a small number of patients in this group the figures are not reliable). In the patients with squamous carcinoma the highest 5-year survival (almost 80.4%) was stated.

Adult↗

[Squamous cell carcinoma].

Squamous cell carcinoma of the skin is common skin malignancy arising from malignant proliferation of the keratinocytes of the epidermis. Chronic exposure to ultraviolet radiation in sunlight is the most important risk factor for squamous cell carcinoma. Early diagnosis and appropriate treatment provide the best opportunity to cure cutaneous squamous cell carcinomas. Although it is locally invasive, squamous cell carcinomas usually remain localized and can be cured by a variety of techniques. Surgical excision is the most broadly used treatment for high-risk squamous cell carcinoma. It is well-tolerated, extremely effective, and the completeness of the procedure can be evaluated through histologic assessment of the specimen's margins. About 10 percent of squamous cell carcinomas in Japan spread to regional lymph nodes or more distant sites with a relatively poor outcome. Five-year cure rates are reported to be 85 to 80 percent for Japanese patients with squamous cell carcinomas, respectively. Recommendations for surgical margins vary depending upon the risk of local recurrence, especially; squamous cell carcinomas with perineural extension also need more extensive procedures. Patients with clinically enlarged lymph nodes may require radiographic imaging, fine needle aspiration, or lymph node biopsy. Depending upon the results of these tests, regional lymph node dissection may be done. Recently the sentinel lymph node biopsy technique is being evaluated for its ability to detect microscopic involvement in patients with high-risk patients who have no clinical evidence of lymph node metastasis. The occurrence of regional lymph node metastases places the patient at increased risk for the subsequent development of distant metastases. Distant metastases are associated with a markedly increased risk of disease-related mortality. Systemic chemotherapy has been to limited benefit in patients with disseminated squamous cell carcinoma patients. In Japanese patients with distant metastases, the five-year survival rate is about 10 percent. The ability of current chemotherapy protocols to increase the cure ratio in squamous cell carcinoma is still controversial.

Antineoplastic Agents↗

Incidence of squamous metaplasia in large bronchi of Japanese lungs: relation to pulmonary carcinomas of various subtypes.

The incidence of bronchial squamous metaplasia in Japanese lungs was investigated in order to clarify the significance of this lesion for the development of lung cancer of various histological subtypes. The bronchi of 104 and 32 lungs resected, respectively, for primary or metastatic tumors were step-sectioned and examined histologically. The incidence of squamous metaplasia was particularly high (83% of cases, 8-11% of sections) in male lungs bearing primary squamous or small cell carcinoma whereas it was low (43% of cases, 3% of sections) in lungs of both sexes with adenocarcinoma, the latter figures being about the same as those for lungs with secondary metastatic tumors. Although the overall incidence of lung squamous metaplasia in Japanese is much lower than in the U.S., the present data demonstrate a high level in association with squamous or small cell carcinoma, directly comparable to that of Americans. However, atypical metaplasia, or dysplasia, was encountered much less frequently than in the U.S. A topographical study of 7 minute or small squamous cell carcinomas revealed 3 to have adjacent and 2 to have nearby areas of squamous metaplasia. However, 2 cases were found to be completely free of squamous metaplastic lesion. Thus, squamous metaplasia may be associated with the development of squamous cell carcinoma but would appear not to be an obligatory step in the development of this neoplasm.

Bronchi↗

[A study on the association between glandular dysplasia and cervical squamous neoplasia in surgical specimens].

To clarify the pathogenesis of cervical adenocarcinoma, we studied the biological properties of glandular dysplasia (GD). The coexistence of squamous neoplasia with cervical adenocarcinoma has been demonstrated. We analyzed the incidence of the coexistence of GD with squamous neoplasia in this study. Materials were surgically removed uterine cervix specimens (n = 142), 52 benign disease cases, 19 squamous dysplasias of the uterine cervix, 66 squamous cell carcinomas of the uterine cervix and 5 cervical adenocarcinomas. Diagnosis of GD was based on the general rules for clinical and pathological management of uterine cervical cancer and Ng's criteria (1983). We divided GD into two types: I: endocervical type, and II: endometrioid type. These fell into subtypes, a (mild) and b (severe) based on the observed degrees of cell atypia. 1. GD coexisted in 17.3% of benign disease cases, 15.8% of squamous dysplasias, 24.2% of squamous cell carcinomas and 100% of cervical adenocarcinomas. 2. GD Ib and IIb were not found in any of the benign disease cases, but were present in 15.8% of squamous dysplasias, 13.6% of squamous cell carcinomas and 100% of cervical adenocarcinomas. If GD was defined as only Ib and IIb, GD coexisted with squamous neoplasia in this study. Our results support the theory that both cervical squamous atypia and cervical glandular atypia are derived from reserve cells.

Adenocarcinoma↗

Survival and staging characteristics for non-squamous cell malignancies of the maxillary sinus.

OBJECTIVE: To characterize the clinical behavior of non-squamous cell cancer of the maxillary sinus. METHODS: Cases of non-squamous cell maxillary sinus malignancy during 1988 through 1998 were extracted from the Surveillance, Epidemiology, and End Results database. Data for histologic type of tumor, tumor stage, and survival were analyzed using the Kaplan-Meier method to determine mean, median, and 5-year survival statistics for the overall cohort and for individual histologic types of tumor. The effect of tumor stage on overall survival was assessed. To determine relative survival, the non-squamous cell group was compared with a second group of patients with squamous cell carcinoma, matched according to age at diagnosis, year of diagnosis, and T stage. RESULTS: One hundred eighty-eight cases of non-squamous cell malignancy were identified. The mean patient age was 57.8 years, and 143 patients (76%) presented with T3 or T4 tumors. There were 31 adenocarcinomas, 64 adenoid cystic carcinomas, 15 mucoepidermoid carcinomas, 22 melanomas, 45 sarcomas, and 11 undifferentiated carcinomas. The overall mean survival was 63.4 months, and 5-year survival was 45.6%. Adenoid cystic carcinoma exhibited the best mean survival (79 months), whereas melanoma and undifferentiated carcinoma exhibited poor mean survivals (30.3 and 12.8 months, respectively). T stage did not statistically affect overall survival (P =.86). Survival for patients with non-squamous cell cancer was substantially better than survival for the matched group with squamous cell carcinomas (mean survival, 41.5 months; 5-year survival, 27.4%). CONCLUSIONS: Patients with non-squamous cell carcinoma of the maxillary sinus typically present with advanced T stage but have significantly better survival than patients with similar-stage squamous cell carcinoma of the maxillary sinus. T stage has less effect than histologic type of tumor on prognosis in non-squamous cell carcinoma of the maxillary sinus.

Adenocarcinoma↗

[Case report of a basaloid squamous epithelial carcinoma of the oropharynx: clinical and histopathologic markers of an aggressive tumor entity].

BACKGROUND: Basaloid squamous cell carcinoma is a variant of squamous cell carcinoma which is located predominantly in the upper aerodigestive tract. The cardinal histopathologic feature is a biphasic cellular pattern of basaloid and squamous components in a close relationship. Major differential diagnoses include adenoid cystic, adeno, squamous, adenosquamous, and basal cell carcinomas. This entity may commonly pose diagnostic difficulties, especially on small biopsy material, if only the basaloid component of the tumor is included. CASE REPORT: A tumor of the oropharynx (T2) was detected in a 61-year-old man. After endoscopic biopsy, this tumor was histologically identified as an adenocarcinoma. A very rapid tumor growth became obvious during the patient's staging. After pharyngectomy and neck dissection, the histopathological diagnosis was corrected to a basaloid squamous cell carcinoma. The definite diagnosis was not made on biopsy material, because only the basaloid component of the tumor was included. DISCUSSION: Basaloid squamous carcinoma is a biologically aggressive tumor with high proliferative activity and a propensity to destructive local growth and early regional and distant metastasis. Literature predominantly indicates that basaloid squamous cell carcinoma is an aggressive variant of squamous cell carcinoma and is prognostically worse than the regular squamous cell carcinoma. CONCLUSION: Because of the aggressive biological behavior of basaloid squamous cell carcinoma, radical surgery combined with radiation and chemotherapy is the treatment of choice.

Biopsy↗

Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium.

Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa.

Animals↗

Evaluation of squamous cell carcinoma antigen as a new marker for lung cancer.

Carcinoembryonic antigen (CEA) is the only tumor marker of proven, although limited, value for the management of patients with non-small cell lung cancer (NSCLC). The authors have prospectively assessed the potential value of a new tumor marker, squamous cell carcinoma antigen (SCC Ag), in a large series of patients with advanced lung cancer (LC). Squamous cell carcinoma antigen and CEA levels were measured in 382 healthy persons (N1 group), 90 patients with benign pulmonary diseases, and 291 patients with LC (129 with SCLC and 162 with NSCLC, including 96 with squamous LC). Carcinoembryonic antigen levels were higher in smokers than in nonsmokers, but smoking habits did not influence the serum concentrations of SCC Ag. Elevated values (above the 95th percentiles of N1, i.e., 7.5 ng/ml for CEA and 3.0 ng/ml for SCC Ag) were observed in 11.1% of patients with benign pulmonary diseases for both markers. Carcinoembryonic antigen was more sensitive than SCC Ag, even for squamous LC (56% versus 35% of elevated values, P less than 0.01). The specificity toward squamous LC was better, however, for SCC Ag, for which levels were elevated in only 8.5% of SCLC and in 18% of other forms of NSCLC, compared with 49% and 55%, respectively, for CEA. Moreover, measurement of SCC Ag and CEA levels did not give redundant information: thus, in squamous LC and SCC Ag level was elevated in 32% of the patients with a normal CEA level, increasing from 57% to 71% the proportion of patients with at least one elevated marker. Lastly, elevation of CEA or SCC Ag levels was an adverse prognostic factor in squamous LC (P = 0.05 for CEA; P = 0.07 for SCC Ag). In conclusion, SCC Ag appears to be worthwhile of further investigation in squamous LC. The authors found that this new marker provided additional information on CEA and that it was more specific for squamous LC than CEA.

Adolescent↗

Involucrin, a marker of squamous and urothelial differentiation. An immunohistochemical study on its distribution in normal and neoplastic tissues.

Involucrin is a soluble protein precursor of the cross-linked envelope present in the submembranous zone of human stratum corneum, and subsequently demonstrated in stratified squamous epithelia. The immunoperoxidase technique was used to assess the distribution of involucrin in 107 normal and 318 abnormal tissues. With few exceptions, involucrin was restricted to squamous epithelia, urothelium, some skin appendages and thymic Hassall's corpuscles. In normal squamous epithelium and normal urothelium, staining was most intense in the superficial layers where it was concentrated at the cell periphery and gradually decreased toward the basal layer. This orderly staining pattern was maintained in benign squamous and urothelial lesions and in grade I papillary urothelial carcinomas. Higher grade papillary urothelial carcinomas, infiltrating urothelial and squamous carcinomas, and in situ urothelial and squamous carcinomas demonstrated abnormal staining patterns for involucrin that are described. Foci of squamous differentiation in adenocarcinomas and other epithelial malignancies stained intensely for involucrin. Brenner tumours of the ovary and Walthard rests of the fallopian tube, lesions of uncertain histogenesis but possibly urothelial-related, also stained for involucrin. Results of this study suggest that involucrin is a sensitive and specific marker for squamous and urothelial differentiation, staining patterns for involucrin may be helpful in distinguishing benign from malignant urothelial and squamous lesions, and presence of involucrin may be helpful in determining the histogenesis of selected lesions.

Carcinoma in Situ↗

Study of human papillomavirus infection in patients with anal squamous carcinoma.

PURPOSE: The purpose of this study was to determine the incidence of human papillomavirus deoxyribonucleic acid (HPV DNA) in anal squamous carcinoma. METHODS: HPV DNA in situ hybridization for HPV Types 6, 11, 16, 18, 31, 33, and 35 was performed on the formalin-fixed, paraffin-embedded tissue from 53 perianal and anal squamous carcinomas and 10 controls. RESULTS: HPV DNA sequences were identified in 18 of 53 anal squamous carcinomas (34 percent). All 10 controls were negative for HPV DNA. Of the 18 positive patients, 10 were perianal squamous carcinomas, and 8 were anal canal squamous carcinomas. Six of the perianal carcinomas were positive for HPV Types 6 and 11. The remaining four perianal carcinomas and all eight of the anal canal carcinomas were positive for HPV Types 16 and 18. CONCLUSION: HPV DNA sequences can be identified in anal squamous carcinomas. Anal squamous epithelium is another site where HPV infection may carry a risk for malignant transformation. One-third of anal squamous carcinomas may be associated with prior HPV infection. Patients with anogenital HPV infection should be routinely screened for anal squamous lesions.

Aged↗

Outcome of HIV-infected patients with invasive squamous-cell carcinoma of the anal canal in the era of highly active antiretroviral therapy.

PURPOSE: Before the development of highly active antiretroviral therapy for the treatment of HIV infection, HIV patients diagnosed with invasive squamous-cell carcinoma of the anal canal carried a very poor prognosis. This study was designed to determine the outcome in a similar group of patients in the era of highly active antiretroviral therapy. METHODS: HIV-positive patients treated for invasive squamous-cell carcinoma of the anal canal at the University of Texas Medical Center affiliated hospitals from 1980 to 2001 were identified from operative data and cancer registries. We reviewed these records and collected data regarding age, CD4 count, highly active antiretroviral therapy, cancer treatment, complications, and survival. The patients were divided into two groups based on the presence or absence of highly active antiretroviral therapy and compared using a Kaplan-Meier approach. RESULTS: Fourteen patients with HIV and invasive squamous-cell carcinoma of the anal canal were identified. Six were in the prehighly active antiretroviral therapy group and eight in the highly active antiretroviral therapy group. All were considered for treatment with chemotherapy and radiation. In the prehighly active antiretroviral therapy group, one patient refused therapy and three were unable to complete the squamous-cell carcinoma therapy as planned because of complications. Four of eight highly active antiretroviral therapy patients were unable to complete the squamous-cell carcinoma therapy as planned. The prehighly active antiretroviral therapy patients had a mean age of 40 years and a mean CD4 count of 190 at the time of diagnosis. The highly active antiretroviral therapy patients had a mean age of 44 years and a mean CD4 count of 255 at the time of diagnosis. The 24-month survival was 17 percent in the prehighly active antiretroviral therapy group and 67 percent in the highly active antiretroviral therapy group (P = 0.0524). All six patients in the prehighly active antiretroviral therapy group died with active squamous-cell carcinoma vs. two in the highly active antiretroviral therapy group. Four of the remaining six patients had no evidence of active squamous-cell carcinoma at the last follow-up visit. CONCLUSIONS: A review of patients with HIV and invasive squamous-cell carcinoma of the anal canal suggests a trend toward a higher CD4 count at the time of diagnosis and improved survival in patients receiving highly active antiretroviral therapy. In this new era, HIV-positive patients should be on highly active antiretroviral therapy. If not, highly active antiretroviral therapy should be initiated, and standard multimodality therapies for invasive squamous-cell carcinoma of the anal canal are recommended.

Adult↗

High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions.

PURPOSE: The purpose of this video is to illustrate the use of high resolution anoscopy in the diagnosis and treatment of anal high-grade squamous intraepithelial lesions. METHODS: Five patients with anal dysplasia were examined in the operating room with acetic acid and the operative microscope. Lugol's solution was used selectively. Acetic acid is generously applied to aide in the recognition of high-grade squamous intraepithelial lesions. Acetowhite regions are examined under the operative microscope to further distinguish lesions as either low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions. Acetowhite lesions with specific vascular characteristics like punctuate vessels or honeycomb patterns are highly suggestive of high-grade disease. These lesions are selectively destroyed under direct visualization with an effort to maintain normal mucosa and skin to prevent stenosis. Some pigmented lesions contain high-grade squamous intraepithelial lesions; the operative microscope is used in this setting to look for the vascular characteristics of high-grade disease. RESULTS: The video reports five male patients treated for high-grade squamous intraepithelial lesions with the aide of high resolution anoscopy. There were no intraoperative or postoperative complications. All lesions suspicious for high-grade squamous intraepithelial lesions based on observed vascular patterns were confirmed as such with permanent histopathology. CONCLUSION: The use of acetic acid and the operative microscope with selective use of Lugol's solution accentuates the visual characteristics of high-grade lesions, enhancing the surgeon's ability to target treatment to high-grade squamous intraepithelial lesions. High resolution anoscopy is useful in the targeted treatment of high-grade squamous intraepithelial lesions.

Anus Neoplasms↗

Numerical aberrations of chromosomes 7, 9 and 17 in squamous cell and transitional cell cancer of the bladder: a comparative study performed by fluorescence in situ hybridization.

PURPOSE: Since squamous cell differs from transitional cell cancer regarding histopathology, clinical outcome and etiology, the underlying genetic effects of these 2 tumor types may also be different. We compared numerical aberrations of chromosomes 7, 9 and 17 in bilharzial squamous cell carcinoma, and bilharzial and nonbilharzial transitional cell carcinoma by fluorescence in situ hybridization, and correlated the findings to p53 positivity of the 3 tumor types. MATERIALS AND METHODS: Cystectomy for invasive bladder cancer was performed in 169 men and 51 women with a mean age of 54.8 years (range 28 to 83). Of the 220 patients 100 (45.4%) had histologically verified bilharzial squamous cell carcinoma, 61 (27.7%) bilharzial transitional cell carcinoma and 59 (26.8%) nonbilharzial transitional cell carcinoma. Using fluorescence in situ hybridization cystectomy specimens were evaluated for numerical aberrations of chromosomes 7, 9 and 17, and p53 detection was performed by immunohistochemistry. RESULTS: Aberrations of chromosome 7 were observed in 79% of the bilharzial squamous cell carcinoma specimens, and 100% and 93.2% of bilharzial and nonbilharzial transitional cell carcinoma specimens, respectively (p = 0.00011). Aberrations of chromosome 9 were seen in 92% of squamous cell carcinoma specimens but in only 52.4% and 60.9% of bilharzial and nonbilharzial transitional cell carcinoma, respectively (p < 0.00001). Aberrations of chromosome 17 were found in only 29% of squamous cell carcinoma specimens, compared to 83.6% and 84.7% aberrations of chromosome 17 in both transitional cell carcinoma groups, respectively (p < 0.00001). The p53 over expression was similar in all 3 tumor types with 82% for squamous cell carcinoma, and 73.7% for bilharzial and 81.3% for nonbilharzial transitional cell carcinoma (not significant, p = 0.5285). CONCLUSIONS: Our data show clear differences between chromosomal patterns of invasive bilharzial squamous cell carcinoma and invasive bilharzial or nonbilharzial transitional cell carcinoma but similar frequencies of p53 over expression in all 3 tumor types. However, aberrations of chromosome 9 were observed in all analyzed groups, which confirms the 2 pathways in the oncogenesis of squamous cell and transitional cell carcinoma at the cytogenetic level as suggested by molecular studies.

Adult↗

Assessment of cervical cancer radioresponse by serum squamous cell carcinoma antigen and magnetic resonance imaging.

OBJECTIVE: To investigate the possibility of objective clinical assessment of the radioresponse of cervical cancer via determination of serum squamous cell carcinoma antigen levels and magnetic resonance imaging (MRI)-based estimation of tumor shrinkage. METHODS: The cases of 60 patients undergoing definitive radiotherapy for cervical squamous cell carcinoma (stage I-II: n = 20; stage III-IV: n = 40) were reviewed. Measurements of serum squamous cell carcinoma antigen levels (n = 60), estimated tumor volume on preradiotherapy MRIs (n = 60), and evaluated tumor shrinkage on postradiotherapy MRIs available (n = 30) were taken. The relation between postradiotherapy squamous cell carcinoma antigen level 2 months after the start of radiotherapy and disease recurrence was investigated. Regression analysis of tumor volume measured on MRIs was used to estimate the extent of tumor shrinkage 2 months after the start of radiotherapy. RESULTS: Preradiotherapy squamous cell carcinoma antigen levels correlated significantly with preradiotherapy tumor volumes. Recurrence was identified in 27 patients as distant (n = 19), distant and local (n = 1), local (n = 5), or regional (n = 2). Of 51 patients with elevated preradiotherapy squamous cell carcinoma antigen levels, 33 achieved normalized levels after radiotherapy. Squamous cell carcinoma antigen normalization was associated with a higher recurrence-free survival rate at 2 years (74.3%) than that associated with nonnormalization of squamous cell carcinoma antigen (5.6%, P <.001). The extent of shrinkage ranged from 61% to 100%, and there was no local recurrence. CONCLUSION: Postradiotherapy squamous cell carcinoma antigen status is a useful indicator of clinical outcome, particularly about tumor recurrence. It is not, however, useful for assessing response to radiotherapy. Magnetic resonance imaging is useful for obtaining an objective assessment of radioresponse.

Antigens, Neoplasm↗

Cytokeratin expression in preneoplastic lesions and early squamous cell carcinoma of the bronchi.

Cytokeratins are expressed in varying combination in the course of differentiation of epithelial cells and tumor cells. This is the first report of systematic immunohistochemical (ABC-method) investigations concerning the expression of different cytokeratin types (KL 1, CK 4, 10 and 17) within the transformation of the bronchial mucosal epithelium with epithelial hyperplasia to potential preneoplasia and early squamous cell carcinoma of the lung. In bioptical obtained specimens from 35 patients, 63 areas with diagnosis of regular bronchial mucosa (n = 10), basal cell hyperplasia (n = 9), goblet cell hyperplasia (n = 10), squamous cell metaplasia (n = 11), dysplasia I-III (n = 13), carcinoma in situ in the border zone of squamous cell carcinoma (n = 10) and in 5 surgically obtained specimens with findings of an early squamous cell carcinoma of the bronchus (n = 5), the expression of different cytokeratin types was investigated. The specimens were fixed in formalin and embedded in paraffin for lightmicroscopical and immunohistochemical investigations (ABC-method). KL 1 was detected in all regular and pathological mucosal epithelia, CK 4 in basal cells, squamous cell metaplasia, potentially preneoplastic changes and early squamous cell carcinoma of the bronchus. CK 10 was expressed only in early squamous cell carcinoma of the bronchus, and CK 17 in varying quantity in hyperplastic, preneoplastic and cancerous lesions of the bronchial mucosa. Our results reveal an increasing expression of squamous epithelial type-cytokeratins (CK 4, CK 17) in hyperplastic and metaplastic lesions of the bronchial mucosa. In dysplastic lesions and carcinomata in situ, a quantitative, as well as qualitative decrease of the CK 4- and CK 17-expression with a heterogeneous expression pattern for CK 17 was found. The heterogeneous neo-expression of CK 10 in early squamous cell carcinoma of the bronchus has to be emphasized.

Bronchial Neoplasms↗

Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase activity and COX-2 as potential markers.

Distinguishing keratoacanthoma from squamous cell carcinoma is a persistent issue in pathology practice. Solitary keratoacanthoma is a self-limiting lesion as opposed to rather aggressive clinical behavior of squamous cell carcinoma. Several markers were studied to understand their biology and to separate these two lesions on a firm basis, but without much success. In this study, we plan to utilize recent markers such as telomerase activity and cyclooxygenase-2 (COX-2) along with more established marker p53 in understanding the biologic differences between keratoacanthoma and squamous cell carcinoma. We studied 17 well to moderately differentiated squamous cell carcinoma and 24 early proliferative phase keratoacanthoma by immunohistochemistry for the expression of p53 protein, COX-2 and telomerase activity. Higher telomerase activity was found in 11/17 squamous cell carcinoma (65%) compared to 4/24 (17%) of keratoacanthoma. Similarly, stronger expression of p53 and COX-2 was detected in 12 (71%) and 11 (65%) cases of squamous cell carcinoma compared to 2 (8%) and 2 (8%) cases of keratoacanthoma respectively. A highly significant 'P' value was obtained for telomerase activity (0.001), p53 (0.000), and COX-2 (0.001). Telomerase activity, COX-2, and p53 expression provide evidence that keratoacanthoma and squamous cell carcinoma are indeed distinct entities and also help in discriminating these two lesions, which closely resemble each other on conventional morphology. Although these markers present new insights into the biologic variation of keratoacanthoma and squamous cell carcinoma, they are of limited value for routine application in histological distinction of these two lesions. The differential expression of markers also explains the sustained proliferation observed in squamous cell carcinoma, compared to a shorter lifespan and involution in keratoacanthoma.

Adolescent↗

TP53 polymorphism of exon 4 at codon 72 in cutaneous squamous cell carcinoma and benign epithelial lesions of renal transplant recipients and immunocompetent individuals: lack of correlation with human papillomavirus status.

A common polymorphism at codon 72 of exon 4 encoding either arginine or proline has been shown to confer a susceptibility to the development of skin tumor in renal transplant recipients. Moreover, this polymorphism may affect proteolytic degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and represent a risk factor for human-papillomavirus-induced carcinogenesis. In this study, we analyzed the human papillomavirus presence and the TP53 allele distribution in cutaneous squamous cell carcinoma of renal transplant recipients and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant recipients with no history of skin cancer, 51 squamous cell carcinomas from immunocompetent patients, and 29 blood samples from immunocompetent individuals without skin cancer were investigated. Human papillomavirus DNA was detected using polymerase chain reaction performed with two pairs of primers (MY09-MY11 and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA was detected in 64% of squamous cell carcinoma and 79% of benign epithelial lesions from renal transplant recipients (NS) and only in 37% of squamous cell carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human papillomavirus types were predominant in squamous cell carcinoma from both renal transplant recipients and immunocompetent patients. Rate of arginine homozygosity in squamous cell carcinoma from renal transplant recipients was significantly higher (83%) than in immunocompetent patients with or without squamous cell carcinoma (60% and 59%, respectively). Our results suggest that TP53 arginine/arginine genotype could represent a potential risk factor for the development of squamous cell carcinoma in renal transplant recipients compared to immunocompetent patients. No association between TP53 arginine/arginine genotype and human papillomavirus status could be determined, however.

Carcinoma, Squamous Cell↗