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[mRNA expression of RASSF1A in esophageal squamous cell carcinoma and clinical significance thereof].

OBJECTIVE: To investigate the mRNA expression of the new tumor suppressor gene, RASSF1A, in esophageal squamous cell carcinoma and its biological value. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of RASSF1A in the tumor tissues, tissues near tumor, and normal tissues, all obtained during operation, from 66 esophageal squamous cell carcinoma patients. RESULTS: The deletion rates of RASSF1A mRNA expression were 42.4% (28/66), 15.2% (10/66), and 0 in the tumor tissues, tissues near tumor, and normal tissues respectively. The deletion rates of RASSF1A mRNA expression in patients with lymph node metastasis was 61.1%, significantly higher than that of the patients without lymph node metastasis (20.0%, chi(2) = 11.323, P < 0.01); The deletion rates of RASSF1A mRNA expression in the esophageal squamous cell carcinoma at the advanced stages (stages III - IV) was 61.5%, significantly higher than that in the esophageal squamous cell carcinoma at the early stages (stages I - II, 30.0%, chi(2) = 6.417, P < 0.01). The deletion rages of RASSF1A mRNA in the highly, moderately, and lowly differentiation tumors were 38.5% (10/26), 38.5% (10/26), and 57.1% (8/14) respectively, However, there was no significant association between the differentiation degree of tumor and the grade the deletion rages of RASSF1A mRNA (chi(2) = 1.576, P = 0.455). CONCLUSION: The deletion of the mRNA expression of RASSF1A, a tumor suppressor gene, may play an important role in the tumorigenesis and influences the prognosis of esophageal squamous cell carcinoma.

Adult↗

[Study of p16INK4/CDKN2 gene homozygous deletions and point mutation in squamous cell carcinoma of buccal mucosa].

OBJECTIVE: To explore the correlation between homozygous deletions and mutation of p16 gene and the carcinogenesis and progression of squamous cell carcinoma of buccal mucosa. METHODS: Thirty buccal cancers, 10 leukoplakias and 8 buccal mucosas were involved. DNA was extracted from the tissues. PCR was used to analyses homozygous deletion of p16 gene. PCR-SSCP-DNA sequencing was performed to detect the point mutation of p16 gene. Immunohistochemical techniques were used to detect the expression of P16 protein. RESULTS: Gene deletions and point mutations were not found in leukoplakia and normal buccal mucosa. Gene deletions were found in 7 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (23.3%), while point mutations were found in 5 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (16.7%). Sequencing analysis showed that 5 cases point mutations were missense mutations, occurred on exon 2. Three cases occurred in the same point, codon 99 (GAT --> AAT). The result of immunohistochemical stains showed that 11 out of 12 cases gene inactivation did not expressed P16 protein. CONCLUSION: Homozygous deletion and point mutation of p16 were the main pattern of gene inactivation in squamous cell carcinoma of buccal mucosa. There was a closely correlation between p16 gene inactivation and the carcinogenesis of squamous cell carcinoma of buccal mucosa.

Carcinoma, Squamous Cell↗

FDG-PET in the initial staging of squamous cell oesophageal carcinoma.

UNLABELLED: Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. AIM: of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophageal carcinoma. PATIENTS, METHODS: In 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. RESULTS: In 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) +/- 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). CONCLUSIONS: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma.

Aged↗

Targeted killing of squamous carcinoma cells by a monoclonal antibody-peplomycin conjugate which recognizes the EGF receptor.

We determined in vitro the antitumor activity of a conjugate prepared by binding a monoclonal antibody (B4G7), which recognizes the human epidermal growth factor (EGF) receptor, with peplomycin (PEP), which is an antitumor agent effective against squamous cell carcinoma. This B4G7-PEP conjugate was prepared by coupling of B4G7 and carboxymethylpeplomycin active ester. The conjugate killed A431 cells of squamous cell carcinoma which overexpress EGF receptors at lower concentrations than PEP alone. On the basis of its IC50, the conjugate was six times more potent than PEP alone. A simple mixture of B4G7 and PEP was as effective as PEP alone in cytotoxicity. The addition of ten times the amounts of B4G7 to this conjugate decreased its cytotoxicity. When other squamous cell carcinoma cell lines with different levels of EGF receptors (NA, Ca9-22, TE-1, TE-8) were treated with the conjugate, cells were killed dose-dependently and the cytotoxicity was dependent on the number of EGF receptors. When each squamous cell carcinoma cell line was treated with a control conjugate prepared by combining PEP with mouse IgG instead of B4G7, no cytotoxicity was observed. These results indicate that B4G7-PEP will be a useful weapon in multidisciplinary treatment which utilizes the EGF receptor, as these receptors are detected in a higher incidence in squamous cell carcinoma.

Antibiotics, Antineoplastic↗

Monoclonal antibody (G10) to a common antigen of human squamous cell carcinoma: binding of the antibody to the H type 2 blood group determinant.

The IgM monoclonal antibody G10 was raised against the human squamous cell carcinoma (SCC) cell line UM-SCC-1. In initial screening against cultured cells, G10 bound to 2 SCC lines (UM-SCC-1 and UM-SCC-13) and 1 pancreatic carcinoma line (UM-PAd-1) but not to cultured fibroblasts (WI-38), ovarian carcinoma cells (SK-OV-3), or malignant melanoma cells (SK-MEL-28 and MeWo). In subsequent tests against cultured cell lines, G10 gave positive reactions with 30 of 33 SCC lines but only 4 of 29 non-SCC lines. The non-SCC lines that bound G10 were UM-PAd-1, 2 transitional cell carcinoma lines (T24 and RT4), and 1 melanoma line (SK-MEL-22). When tested against cultures derived from normal skin or mucosa, G10 was reactive with the epitheloid squamous cells but not with the fibroblasts in each culture. The antigen defined by antibody G10 was stable to fixation with Formalin, and its distribution in tissue sections was examined with the use of immunoperoxidase assays. All SCC biopsy specimens examined in this way were reactive with antibody G10. In similar tests against sections of fixed normal tissues, G10 stained the superficial squamous cells of the epidermis and the basal and suprabasal layers of mucosal squamous epithelial cells from the esophagus. All layers of the laryngeal epithelium were positive. Endothelial cells and certain glandular cells were also positive for G10 binding. G10 agglutinated human red blood cells of all blood groups except those from individuals of the Bombay group (Oh) who lack the H blood group determinant. Against defined oligosaccharides, G10 bound strongly only to the monofucosyl H type 2 structure and was slightly cross-reactive with the synthetic difucosyl H type 2 or Y structure. These results are consistent with previous reports of blood group antigen tissue distribution and indicate that the H type 2 determinant is expressed by all or nearly all mucosal squamous cancers. Less frequent expression by cells of other tumor types may correlate with tissue-specific activation of the H gene-specified fucosyltransferase.

ABO Blood-Group System↗

UV radiation-induced tumors in haired mice: identification as squamous cell carcinomas.

The most common tumor induced by UV radiation in haired mice is considered to be a fibrosarcoma on the basis of its presentation as a nodule in the skin and on the basis of a spindled appearance upon light microscopic examination. A squamous cell carcinoma is thought to be a much less common tumor. In the present report this concept was reevaluated in mammary tumor virus-free C3H/HeNCr (C3H-) mice. From first appearance, almost all lesions upon gross morphologic examination have an epidermal component and initially are similar to solar keratoses in humans. The lesions then become nodular and eventually develop central ulceration, often with a rolled border characteristic of squamous cell carcinomas. The morphology upon light microscopic examination ranged from well-differentiated squamous cell carcinoma to a poorly differentiated spindle cell neoplasm. Occasionally, variable patterns of squamous differentiation were seen in the same lesion. Immunoperoxidase examination with a polyclonal antikeratin serum demonstrated the presence of keratin in 84 of 87 tumors. Frequent, poorly formed desmosomes were found on ultrastructural examination. These tumors usually had a regressor phenotype upon transplantation into recipients. In conclusion, almost all UV radiation-induced tumors in C3H- mice are squamous cell carcinomas, and these tumors are usually antigenic.

Animals↗

Ultrastructural localization of a new surface membrane antigen (SQM1) related to squamous differentiation.

Normal squamous epithelial cells readily undergo terminal differentiation in culture and are commonly used in differentiation studies. Several intracellular markers of squamous differentiation such as keratin, involucrin, transglutaminase and cholesterol sulfate have been well-studied and described by other workers. We have recently reported a surface membrane antigen in squamous carcinoma of the head and neck antigen in squamous carcinoma of the head and neck which is recognized by a murine monoclonal antibody SQMI. In this paper, we present our studies on the ultrastructural localization of SQMI antigen in cultured squamous epithelial cells using gold-labelled antibody. The cells studied included both normal and cancer cells at different degrees of differentiation. Under both transmission and scanning electron microscopy examination, the SQMI antigen was localized at the membrane surface of cultured cells, particularly at sites of cell-cell interdigitation. No association with desmosomal structure was observed in any of the specimens examined. There was however an association of SQMI antigen with microvilli of cell membrane. No non-specific cytoplasmic localization of SQMI antigen was observed. The intensity of SQM1 antigen revealed by gold-labelling appeared to have a positive correlation with the degree of differentiation of the cells in culture.

Antibodies, Monoclonal↗

Current management of non-squamous carcinoma of the cervix.

The incidence of non-squamous carcinoma of the cervix, relative to squamous cell carcinoma, seems to have been increasing over the past 15 years, and adenocarcinomas currently constitute 10 to 18% of cervical cancers. Uncertainties regarding the clinical behavior and management of women with non-squamous cervical cancer persist. Certain cell types and grade of adenocarcinomas play a role in prognosis and treatment selections. Treatment via irradiation or radical surgery for Stage I, small, garden variety cervical adenocarcinomas will result in excellent survival. Conversely, survival may be poor in early stage non-squamous lesions if they are of high grade or of certain cell types, such as adenosquamous carcinoma. Patients with advanced cancers of other organ systems can now achieve an increase in progression-free interval with neoadjuvant chemotherapy or concomitant irradiation/chemotherapy. Such treatments might also benefit patients with non-squamous cervical cancers.

Adenocarcinoma↗

Serum squamous cell carcinoma antigen in gynecologic malignancies with special reference to cervical cancer.

Squamous cell carcinoma (SCC) antigen was measured by double-antibody radioimmunoassay in the sera of 113 patients with gynecologic malignancies and 30 controls. The mean serum SCC antigen level was 9.24 ng/ml in those with cervical squamous cell carcinoma, 2.15 ng/ml in those with other gynecologic malignancies, and 1.25 ng/ml in controls. With a cutoff value of 2.23 ng/ml (2 SD above the mean of the control group), the rate of SCC antigen elevation was 54% in cervical cancer (78), 14% in vulvar or vaginal cancer (7), 22% in ovarian cancer (18), and 10% in endometrial cancer (10). In cervical squamous cell carcinoma, the rates of elevated SCC antigen level increased with disease advancement in stages 0, I, II, III, and IV, by 13, 50, 53, 78, and 100%, respectively. In early-stage cervical squamous cell carcinoma, SCC antigen was not sensitive enough for screening. However, if elevated, serum SCC antigen levels decreased rapidly after successful surgical treatment. One case with a serum SCC antigen level above 65 multiples of the cutoff value had widespread cancer and postoperative recurrence. In the advanced case, the sensitivity was much higher. In the recurrent case, the positive rate was 73%. Serum SCC antigen level is useful in predicting the prognosis and monitoring the course of cervical squamous cell carcinoma, especially in the detection of a recurrence.

Antigens, Neoplasm↗

Sequential cytologic study of the development of squamous cell carcinoma induced in subcutaneously implanted bronchial autograft of dog.

Squamous cell metaplasias and the development of squamous cell carcinomas caused by carcinogenic polycyclic hydrocarbon exposure of the lumen of grafted dog bronchi were followed by cytology, and were correlated to histologically and ultrastructurally observed changes seen in the biopsy specimens at the same time periods. Cytologic specimens showed a progression from mild atypia of squamous metaplastic cells, to moderate atypia, and to marked atypia before the development of invasive squamous cell carcinoma. Histology obtained by the biopsy specimens revealed findings corresponding to these cytologic changes. In the premalignant phase, squamous dysplasia and carcinoma in situ-like changes were also seen. Ultrastructural findings of the epithelium, such as widened intercellular space, increasing tonofilaments, enlarged nuclei with deep indentations, and prominent nucleoli with microsegregation were characteristic changes in the preneoplastic stages. It was concluded that this method of cytology, reflecting histologic and ultrastructural changes, is a useful experimental tool for the comparative study of premalignant lesions in the human bronchus and their early neoplastic stages.

Animals↗

[Squamous cell carcinoma co-existing vesical leukoplakia--case study and its clinicopathological analysis of the pathogenesis].

A 66-year-old female complained of fever and lumbar pain was diagnosed as the squamous cell carcinoma associated with vesical leukoplakia cystoscopically. Histopathological figures showed various forms of squamous metaplasia, involving squamous cell carcinoma nests within it. Now, the relationship between vesical leukoplakia and squamous cell carcinoma is not obscure. Then the treatment of the leukoplakia has been considered conservatively (fulguration, acidification of the urine and anti-microbials). Now, we can classify the lesions of squamous metaplasias into two types in the urinary bladder. The possibility of the malignant change in the leukoplakia lesions could be suggestive of the histological characteristics; irregularly down growth and disarrangement of the basal cells and/or dispersed basement membrane in rete pegs in the metaplasia.

Aged↗

[Clinical investigation of neuron-specific enolase, squamous cell carcinoma-related antigen and carcinoembryonic antigen in carcinoma of the lung].

Serum levels of neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC antigen) and carcinoembryonic antigen (CEA) were measured in 53 untreated patients with carcinoma of the lung. The positive rates of serum NSE were 17.0% in all patients with lung cancer, 53.8% in small cell carcinoma, 6.7% in adenocarcinoma, 5.0% in squamous cell carcinoma and 0% in large cell carcinoma; 0% in stage I, 14.3% in stage III and 26.7% in stage IV. The positive rates of serum SCC antigen were 45.3% overall, 70.0% in squamous cell carcinoma, 40.0% in adenocarcinoma, 23.1% in small cell carcinoma and 0% in large cell carcinoma; 42.9% in stage I, 57.1% in stage III and 46.7% in stage IV. In comparison with serum CEA, serum NSE and SCC antigen were much more specific in small cell carcinoma and squamous cell carcinoma, respectively. Moreover, serum levels of NSE and SCC antigen changed in parallel with the clinical course during the treatments. In conclusion, serum NSE and SCC antigen were considered to be very useful markers of lung cancer, especially of small cell carcinoma and squamous cell carcinoma, respectively.

Adenocarcinoma↗

[Immunohistochemical studies on epidermal growth factor receptor and the myc oncogene product in squamous cell carcinoma of the uterine cervix].

Recent studies have demonstrated that the amount of epidermal growth factor receptor (EGF-R) is increased in squamous cell carcinoma cells and that the amino acid sequence of EGF-R shows great homology with the v-erb B transforming protein. In this study, we examined the tissue localization of EGF-R and myc oncogene product in normal squamous epithelium, dysplasia, carcinoma in situ, invasive squamous cell carcinoma of the uterine cervix and in metastatic lymph nodes by means of the avidin/biotin immunoperoxidase technique. Normal squamous epithelium was negative for EGF-R and myc product. The lesions of dysplasia and carcinoma in situ had a positive staining for EGF-R, but were still negative for myc product. There were differences in the staining intensity of EGF-R and myc product among the types of invasive carcinoma. Staining for EGF-R and myc product was negative in small cell non-keratinizing carcinoma, whereas strong staining for both EGF-R and myc product was observed in large cell non-keratinizing and keratinizing carcinoma. The intensity of positive staining for EGF-R and myc product declined in the lesions of cancer pearl. Metastatic lymph nodes were remarkably stained for EGF-R and myc product, while non-metastatic lymph nodes were negative for EGF-R and myc product. Our observations suggest that the amplified expression of EGF-R and myc product may accompany the malignant transformation of squamous epithelium of the uterine cervix, together with the metastasis.

Carcinoma, Squamous Cell↗

[Squamous cell carcinoma of the ascending colon--a case report and review of literature].

One case of squamous cell carcinoma of the ascending colon is reported. The patient, a sixty two year old woman, was admitted because of right abdominal pain for three months. A mass, 6 X 5 cm in size, was palpated. 13 cm colonic mucosa destruction was shown by barium enema. Right hemicolectomy was done. A squamous cell carcinoma of the ascending colon was diagnosed by light and electron microscope. Squamous cell carcinoma of the colon is rare. Squamous cell carcinoma and adenoacanthoma, occurring in the colon and upper rectum, comprise 0.5% of all colonic malignancies. 18 cases have been collected in the literature and this case is the first one reported in China. Etiology of squamous cell carcinoma of the large bowel is reviewed.

Carcinoma, Squamous Cell↗

Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder.

Recent incidence data from the United States indicate that transitional cell carcinoma accounts for the vast majority (95%) of bladder tumors in this country, with squamous cell carcinoma (less than 3%) and adenocarcinoma (less than 2%) comprising nearly all the remaining cases. Rates of squamous cell carcinoma and adenocarcinoma were higher in blacks compared to whites, while the reverse was true for transitional cell carcinoma. All three tumors predominated in males, especially transitional cell carcinoma. A population-based case-control study of bladder cancer conducted in 10 geographical areas of the United States identified 43 patients with squamous cell carcinoma and 32 with adenocarcinoma to permit an examination of risk factors. Cigarette smoking was significantly associated with risk of squamous cell carcinoma, with the relative risk rising to 6.1 among smokers of 40 or more cigarettes/day. Significantly elevated risks of squamous cell carcinoma were also associated with a history of 3 or more urinary tract infections (relative risk = 5.7) and with employment as welders and cooks. Risk factors were generally less conspicuous for adenocarcinoma, except for a significant trend with the amount of coffee drinking; however, this finding is based on small numbers and should be interpreted cautiously.

Adenocarcinoma↗

Squamous cell carcinoma of the stomach: report of three cases.

Three primary tumors of the stomach diagnosed as pure squamous cell carcinoma were reexamined with newly prepared multiple sections. In each tumor histological studies revealed minute areas of adenocarcinoma in addition to large areas of squamous cell carcinoma. This finding suggests that some gastric squamous cell carcinomas may be adenosquamous carcinomas with a predominant squamous component. The pathogenesis of primary squamous cell carcinoma of the stomach is discussed with respect to our observations and with due reference to the literature. The aggressive behavior of this tumor is also given attention.

Adenocarcinoma↗

Squamous cell carcinoma of the head and neck at the Massachusetts General Hospital: a comparison of biologic characteristics in men and women.

Little is known about the biologic behavior of squamous cell carcinoma of the head and neck in women. A few recent reports for selected sites have suggested that these tumors may be becoming more common in women. To evaluate potential differences between males and females with squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx and to assess whether the proportion of females with this disease is increasing, the authors have undertaken a retrospective review of 542 consecutive patients treated at our institution from 1962 through 1976. We report here the first detailed comparison of males and females with squamous cell carcinoma of the head and neck, with attention directed to stage at initial presentation, choice of therapy, response to therapy, age distribution, survival, and prevalence of second primary malignancies. It has been widely published that survival for women with squamous cell carcinoma of the head and neck is superior to that for men, and this has been attributed to a difference in the biologic characteristics of the disease between the two sexes. Although overall survival calculations in our series suggested a significantly better survival rate for women than for men, these rates were strongly influenced by the larger proportion of women (64%) who had stage I or II disease, compared with only 50% of men. When survival was compared stage by stage, there was no significant difference in survival between the two sexes. The proportion of females in the combined study population was 35%, increasing from 33% in the first 5 years of the study period to 40% in the last 5 years. Among patients born before 1920, 34% were female compared with 43% of patients born after 1920. Of the 13 patients less than 40 years of age at diagnosis, 62% were female. The rising proportion of women during the 15-year study period, particularly among young patients and those in more recent birth cohorts, strongly suggests that squamous cell carcinoma of the head and neck is increasing among women in this referral population. A review of the literature indicates that this trend began more than 40 years ago.

Adult↗

Monoclonal antibodies to human squamous cell carcinoma of the lung and their application to tumor diagnosis.

Three immunoglobulin G1 monoclonal antibodies, LuCa2, LuCa3, and LuCa4, were produced by fusing murine myeloma NS1 cells with splenocytes obtained from a BALB/c mouse immunized with SK-MES1 cells derived from human squamous cell carcinoma of the lung. These three monoclonal antibodies were shown to recognize different protein antigens on SK-MES1 cells by indirect immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. While the pattern of cell line distribution of antigens recognized by these antibodies was not tumor type specific, their reactivity with tissue and pleural effusion was much more informative than with cell lines. The presence of target antigens in vivo was analyzed by immunoperoxidase staining of frozen tissue sections and immunofluorescence staining of tumor cells in pleural effusions. LuCa2 antibody was reactive with lung squamous carcinoma and adenocarcinoma tumor tissues and pleural effusions, but only infrequently with those of small cell carcinoma. This antibody was also reactive with many tumor tissues from other organs as well as with various normal tissues, including alveoli and bronchus. LuCa3 and LuCa4 antibodies reacted with lung squamous carcinoma in tissues and pleural effusions, but not with lung adenocarcinoma nor with small cell carcinoma. These two antibodies reacted only weakly with normal squamous tissues of the esophagus, skin, and cervix uteri, but not with various other normal tissues. Moreover, LuCa3 had weak reactivity with squamous cell carcinoma tissue of tongue and esophagus, whereas LuCa4 had no reactivity with nonpulmonary tumor tissues. LuCa3 and LuCa4 antibodies should be of clinical interest, because our data suggest that these antibodies may be potentially useful for the diagnosis of the histological type of lung tumor cells in both cancer tissue and pleural effusions.

Antibodies, Monoclonal↗