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PubMed2000

Inverted follicular keratosis of the vulvar skin: a lesion that can be confused with squamous cell carcinoma.

Although seborrheic keratoses of the vulva are described in textbooks, to our knowledge, inverted follicular keratosis has not been reported. A 27-year-old woman underwent an excisional biopsy for a small lesion of the left labium majus. Squamous cell carcinoma was considered in the clinical differential diagnosis. The initial pathologic diagnosis suggested squamous cell carcinoma in situ, and the consultation diagnosis was superficially invasive squamous cell carcinoma. On pathologic examination, a symmetrical, endophytic, epithelial tumor was observed consisting of a proliferation of basaloid cells with many areas of reactive squamous cells showing numerous squamous eddies, focal reactive nuclear atypia, and occasional mitotic figures. After the pathologic diagnosis of inverted follicular keratosis was made, a history of close perineal shaving and total body tanning was obtained. Because inverted follicular keratosis is postulated to be related to follicular injury, it is likely that the trauma of close shaving is a significant etiologic factor. There is less evidence that ultraviolet ray exposure is of etiologic importance.

Adult↗

PubMed2002

Loss of gamma-Catenin expression in squamous differentiation in endometrial carcinomas.

Squamous differentiation occurs in 25 to 50% of endometrial endometrioid adenocarcinomas. In this study, we analyzed the immunohistochemical expression and localization of beta- and gamma-catenin, molecular changes in the beta-catenin gene, and the subcellular localization of the desmosomal component protein, desmoplakin, by laser scanning microscopy in 35 endometrial carcinomas with squamous differentiation. In the glandular component, beta-catenin showed nuclear localization in 10 of 35 (28.5%) samples, whereas in the squamous component, nuclear localization was found in 15 of 35 (42.9%). Of the 15 samples that showed nuclear localization of beta-catenin in the squamous component, seven samples (46.7%) did not express gamma-catenin. The phenomenon was not correlated with mutation in exon 3 region of beta-catenin gene. Furthermore, in these samples, there was diffuse cytoplasmic staining for desmoplakin. These observations have not been reported in other tumors. Our results suggest that unique molecular events, i.e., stimulation of beta-catenin and suppression of gamma-catenin expression, occur within endometrial carcinomas with squamous differentiation.

Adenocarcinoma↗

PubMed2004

Dysregulation of hypoxia inducible factor-1alpha in head and neck squamous cell carcinoma cell lines correlates with invasive potential.

OBJECTIVES/HYPOTHESIS: Tumor hypoxia appears to be closely associated with tumor propagation, malignant progression, and resistance to radiotherapy. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that is upregulated under hypoxic conditions and activates hypoxic adaptation pathways which include neovascularization, erythropoiesis, and glycolysis. Hypoxia inducible factor-1alpha is under tight regulation with undetectable levels of expression in normoxia and robust expression in hypoxia. Mutations that activate oncogenes or inactivate tumor suppressor genes increase the expression of HIF-1alpha. Furthermore, it has been demonstrated that HIF-1alpha is overexpressed in head and neck squamous cell carcinoma and that the degree of expression has predictive and prognostic significance for patients undergoing radiotherapy. The study investigated whether overexpression of HIF-1alpha in head and neck squamous cell carcinoma results from a physiological response to local hypoxia or from oncogenic mutational progression. STUDY DESIGN: Expression of HIF-1alpha under normoxic and hypoxic conditions was evaluated in cell lines derived from head and neck squamous cell carcinoma. Cell lines that were used displayed varying degrees of in vitro invasiveness. METHODS: Hypoxia inducible factor-1alpha expression was detected by Western blot analysis. Cells were treated for 3 hours in 1% oxygen, then re-exposed to normoxia for varying times before lysis and detection of HIF-1alpha. RESULTS: Under normoxic conditions, HIF-1alpha expression was upregulated in invasive cells compared with noninvasive cells, and the degradation of HIF-1alpha following a hypoxic stimulus was blunted in invasive cells as compared with noninvasive cells. CONCLUSION: The authors presented evidence that dysregulation of HIF-1alpha may play a role in the malignant progression of head and neck squamous cell carcinoma. It is likely that dysregulated expression of the transcription factor HIF-1alpha contributes to the invasive properties associated with hypoxia and advanced head and neck squamous cell carcinoma.

Blotting, Western↗

PubMed1982

Metastasis from squamous cell skin cancer of the extremities.

In a series of patients with localized squamous cell skin cancer treated at a cancer center, the incidence of metastasis was 1.4%. A premalignant condition, including thermal burns and irradiation dermatitis, was found in 30% of those patients, and 28% had multiple primary skin cancers. Forty-two of the 106 patients with metastasis had experienced local treatment failures, suggesting that such patients may be at greater risk of metastasis. In all but one instance of metastasis occurring from squamous cell skin cancer of the extremities, the regional lymph nodes were involved. Despite aggressive therapy, the five-year survival of patients with nodal metastasis was only 39%. Extracapsular spread of nodal disease was of grave significance. Based on the experience with metastatic squamous cell skin cancer of the head and neck, it is proposed to evaluate the adjunctive use of preoperative or postoperative irradiation and surgery in the treatment of metastatic squamous cell cancer of the skin of the extremities. Careful follow-up of patients with squamous cell skin cancer is necessary, and the lethal potential for recurrence and regional metastasis must be recognized.

Adolescent↗

PubMed1996

Primary squamous cell carcinoma of the breast.

Primary squamous cell carcinoma of the breast is a rare cancer. Published reports of prognosis are variable, and most studies are case reports of one or a few patients. We report an additional case of squamous cell carcinoma of the breast occurring in a 53-year-old black woman. In reviewing the reported cases of this tumor over the past 20 years, we compared features of this cancer with those of the more common breast adenocarcinoma with squamous metaplasia. When squamous cell carcinoma of the breast is encountered, a skin primary lesion and metastasis from a distant site should be excluded. Prognosis is determined largely by stage and does not differ significantly from the prognosis in breast adenocarcinoma with squamous metaplasia.

Adenocarcinoma↗

PubMed2002

Telomerase activity, telomere length, and apoptosis: a comparison between acquired cholesteatoma and squamous cell carcinoma.

BACKGROUND: Cholesteatoma disease is characterized by accumulation of keratinizing epithelium. Several molecular markers of tumor formation have been found in cholesteatoma (e.g. upregulation of matrix metalloproteinases, c and activation of angiogenesis). Other molecular findings clearly distinguish between cholesteatoma and malignant tumors (e.g., lack of chromosomal instability, intact checkpoint responses). To further distinguish the molecular mechanisms in cholesteatoma from malignant tumors, the authors determined telomerase activity and telomere length in both tissue types. METHODS: To evaluate the role of telomerase activation and telomere length in cholesteatoma, 29 cholesteatoma samples and 9 squamous cell carcinomas were analyzed for telomerase activity and telomere length. In addition, the rate of apoptosis was determined in both groups, using the TdT-mediated dUTP nick end labeling technique. RESULTS: As previously described, a high proportion of squamous cell carcinoma exhibited telomerase activity (6/9, 66%). By contrast, a significantly lower rate of telomerase activity was found in cholesteatoma samples (1/29, 3.4%, p = 0.0002). Despite the differences in telomerase activity, the telomere length was similar in cholesteatoma (mean length 7.43 kb) and in squamous cell carcinoma (mean length 7.99 kb; difference not significant, p = 0.1364). The low rate of telomerase activity in cholesteatoma was accompanied by significantly higher rates of apoptosis in cholesteatoma (mean 30%) compared with squamous cell carcinoma tissue (mean 3%, p = 0.0031). CONCLUSIONS: Taken together, these data show that telomerase activation is a rare event in cholesteatoma and that the absence of telomerase activity is accompanied by high rates of apoptosis in cholesteatoma. It is proposed that the absence of telomerase limits the proliferative capacity of cholesteatoma by induction of apoptosis, whereas the presence of telomerase allows immortal growth of squamous cell carcinoma.

Adult↗

PubMedDate not supplied

Tissue eosinophilic infiltration: a useful marker for assessing stromal invasion, survival and locoregional recurrence in head and neck squamous neoplasia.

UNLABELLED: The assessment of stromal invasion in aerodigestive neoplastic squamous proliferation often poses diagnostic and therapeutic challenges. Eosinophilic infiltration is thought to be an adjunctive histologic criterion in determining tumor aggressiveness and invasion. We investigated whether an eosinophilic infiltration in head and neck squamous cell carcinoma measured in biopsies would aid in predicting tumor invasion, response to treatment, locoregional recurrence, and survival. METHODS: Eighty-seven patients with in situ and invasive squamous cell carcinoma of the head and neck region were evaluated and treated according to their staging. The number of eosinophils per high-power field (eosinophil/HPF), and per 10 high-power fields (eosinophil/10 HPF) at the tumor interface and in tumor tissue, was counted and classified as focally or diffusely present. Each sample was assigned an eosinophilic index of 1-4 based on the number of eosinophils/HPF or 10 HPF. Of 87 patients, 20 patients were followed up after appropriate treatment for locoregional recurrence, distant metastasis, and disease-free survival. RESULTS: Eosinophilic counts were elevated focally and/or diffusely more frequently in invasive squamous cell carcinoma than in noninvasive tumors. The increased eosinophilic counts, specifically > 10/HPF and > 20/10 HPF, were both significantly associated with stromal invasion. Greater than 10 eosinophils/HPF and/or > 20 eosinophils/10 HPF had the highest predictive power for invasion, with sensitivity, specificity, and positive predictive values of 66%, 94%, 96% and 61%, 100%, and 100%, respectively. Eosinophilic counts greater than 20 eosinophils/10 HPF and eosinophilic indices > 2 were virtually diagnostic for tumor invasion. Patients' biopsies with eosinophilic indices < 2 had a better survival (P = 0.0156). Using Cox regression analysis, we found that most patients' biopsies that had eosinophilic indices > 2 recurred locally or regionally. CONCLUSIONS: The elevated eosinophilic counts in biopsies and eosinophilic indices in specimens of squamous cell carcinoma of the aerodigestive tract are a histopathologic marker associated with tumor invasion and a clinical predictor for aggressive tumor biology. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should indicate the need for additional therapeutic measures and close surveillance to detect earlier locoregional recurrence and possible distant metastasis.

Adult↗

PubMed2006

Human papillomavirus triage for young women with atypical squamous cells of undetermined significance.

OBJECTIVE: Human papillomavirus testing is a cost-effective strategy for the management of atypical squamous cells of undetermined significance. Young women have a high prevalence of transient human papillomavirus infections and low incidence high-grade cervical lesions, which may limit the usefulness of human papillomavirus testing in this cohort. We sought to estimate the usefulness of human papillomavirus testing for young women with atypical squamous cells of undetermined significance. METHODS: A retrospective study of women with atypical squamous cells of undetermined significance was undertaken. Reflex human papillomavirus results and pathologic follow-up were evaluated. Age-stratified rates of human papillomavirus positivity, rates of high-grade dysplasia, and sensitivity and specificity were estimated. RESULTS: A total of 1,290 women with atypical squamous cells of undetermined significance cytology were identified. The rate of human papillomavirus positivity decreased with age from 55% for those aged 25 years or younger to 12% for women aged older than 50 years (P < .001). The cumulative rate of high-grade lesions increased with age; 12% for patients aged 25 years or younger compared with 24% for women aged older than 50 years (P = .05). A negative human papillomavirus test more effectively excluded high-grade disease in the young women. No high-grade lesions were detected in the human papillomavirus negative women aged 25 years or younger compared with 3.8% of those aged older than 50 years (P = .04). The sensitivity for detection of high-grade disease was higher in women aged younger than 25 years compared with those aged older than 50 years (100% compared with 50%), whereas specificity was lower (14% compared with 44%). CONCLUSION: Given the high prevalence of human papillomavirus and low occurrence of high-grade lesions in young women with atypical squamous cells of undetermined significance, a human papillomavirus-based triage strategy will result in the referral of a large number of women for colposcopy and may limit its cost-effectiveness. LEVEL OF EVIDENCE: III.

Adolescent↗

PubMedDate not supplied

Expression of the epidermal growth factor receptor in conjunctival squamous cell carcinoma.

PURPOSE: To determine whether the tyrosine kinase epidermal growth factor receptor (EGFR) is expressed in squamous cell carcinoma of the conjunctiva. METHODS: A retrospective, observational case series of 5 patients with biopsy-proven conjunctival squamous cell carcinoma treated at one institution between January 1996 and April 2004. Medical records and tissue specimens from the 5 patients were reviewed. A control specimen of normal conjunctiva was also obtained from one of the 5 patients. Immunohistochemical analysis was performed using antibodies against EGFR. RESULTS: Immunohistochemical staining showed that EGFR expression was moderate to strong in all tissue specimens, both in the normal mucosa and in the in situ and invasive components of the conjunctival squamous cell carcinomas. CONCLUSIONS: An intense expression of EGFR occurs in squamous cell carcinoma of the conjunctiva. Further study is needed to determine whether an EGFR inhibitor that targets this expression would have potential therapeutic benefit in treating squamous cell carcinoma of the conjunctiva.

Adult↗

PubMedDate not supplied

Ocular adnexal pseudo-cyst formation as a characteristic feature of perineural spread in squamous cell carcinoma.

PURPOSE: To report the clinical features in a series of patients with perineural spread of squamous cell carcinoma involving periorbital nerves that presented with clinical and/or imaging evidence of pseudo-cystic transformation along the involved nerves. METHODS: A noncomparative, retrospective chart review of the clinical and imaging findings of patients attending a regional orbital surgery department between 1998 and 2005, presenting with a pseudo-cystic orbital mass on clinical examination and/or imaging, which proved to be due to perineural squamous cell carcinoma on histopathology. RESULTS: The study included 8 male patients with a mean age at referral of 66 +/- 11 years. All cases had associated cutaneous squamous cell carcinoma involving the face or scalp, and, in 4 cases, the primary tumor could be identified in the vicinity of the affected orbit. The duration of the symptoms varied from 5 weeks to 9 years (24 +/- 36 months). Altered sensation, including formication and hypo-esthesia in the V1 and V2 trigeminal division, motor nerve palsies, and ptosis in conjunction with a palpable periorbital mass, were the most common presentations. The cystic tumor deposits were assessed histologically with both hematoxylin and eosin and immunoperoxidase stains (S100 protein for neural structures identification and MNF116 as a keratin marker). This demonstrated malignant squamous epithelium both within and around the wall of the tumor deposit and, in continuity, within the nerve running through the lesion. Some nerves showed substantial areas of fibrosis, representing obliteration of the nerve structure caused by involvement by tumor. Treatment modalities included surgical debulking, exenteration, radiotherapy, and combined chemo-radiotherapy. Mean follow-up was 29 +/- 23 months. Eight patients (87.5%) remain alive, and five of them show no evidence of disease. One patient died after progression of the malignancy. CONCLUSIONS: The presence of a cystic lesion in association with sensory or motor deficit in the periorbital region should suggest a diagnosis of perineural spread from a cutaneous squamous cell carcinoma. Because these patients may present to the ophthalmologist first, an awareness of this entity is of critical importance to avoid the delayed diagnosis seen in half of our cases.

Aged↗

PubMed2006

Molecular basis of posttransplant squamous cell carcinoma: the potential role of cyclosporine a in carcinogenesis.

Cyclosporine (CSA) is a widely used immunosuppressive agent, predominantly for transplant patients. It is well recognized that transplant patients are prone to develop squamous carcinoma of the skin and mucosa, and this high incidence of squamous carcinoma in the transplant population cannot be explained by immunosuppression alone. We hypothesize that CSA may play a significant role in the transformation of normal epidermal squamous cells to carcinoma. CSA is a specific ligand for calcineurin, a ubiquitously expressed cellular serine/threonine phosphatase, that plays important roles in the immune system and cardiac muscles. Using global gene-profiling methods, we studied the short-time CSA effect on the squamous cell line (SCC-015) using Affymetrix human gene chips (Human U133, 2.0 plus chip). Multiple groups of genes were identified to be responsive to CSA treatment, including many genes of unknown functions. We then used reverse transcriptase-polymerase chain reaction and immunoblot analyses to selectively confirm the results from the chips analyses with emphasis on the regulatory molecules important for cellular functions of apoptosis, DNA damage repair, and cellular transformation. This global gene-profiling study indicated that CSA not only functions as an immunosuppressant on the immune system, but also activates/inhibits a wide array of genes important for cell-cycle regulation, apoptosis, and oncogene/tumor-suppressor activation. These functions of CSA on skin and mucosa systems at the molecular level are likely important in the pathogenesis of squamous carcinoma in transplant patients.

Carcinoma, Squamous Cell↗

PubMed1984

Involucrin in squamous and basal cell carcinomas of the skin: an immunohistochemical study.

Involucrin is a precursor of cross-linked protein of human stratum corneum, and its appearance in the upper layers of the epidermis is a function of the normal differentiation of the keratinocyte. Cases of basal cell and squamous cell carcinoma were evaluated for the presence of involucrin using immunoperoxidase techniques on paraffin sections. Basal cell carcinomas were negative for involucrin with staining restricted to squamous horn cysts, while squamous cell carcinomas stained strongly, particularly in large keratinized cells. Cases of squamous cell carcinoma in situ (Bowen's disease) revealed increased staining for involucrin with staining of dyskeratotic cells at all levels in the epithelium. Abnormal patterns of staining were also noted in non-neoplastic epidermis adjacent to carcinomas. Immunohistochemical staining for involucrin identifying abnormal or premature keratinization is a sensitive marker for dyskeratosis in squamous epithelia and may have applications in the histopathologic evaluation of skin specimens.

Basal Cell Carcinoma↗

PubMed1994

Immunohistochemical localization of a novel beta 1 integrin in normal and pathologic squamous epithelia.

The 10.1.2 MoAb reacts with a novel alpha chain that associates with the beta 1 integrin chain and is widely distributed among epithelial and endothelial cells of human adult and fetal tissues. In the epidermis and in other squamous epithelia, alpha 10.1.2 chains are expressed exclusively in the basal cell layer. Here we describe the immunohistochemical localization of alpha 10.1.2 in human epidermis, in other squamous epithelia, as well as in cultured keratinocytes. alpha 10.1.2 chain localization has also been investigated in a variety of non-neoplastic and neoplastic lesions of the skin, the uterine cervix, and the lung. We show that alpha 10.1.2 chains retain their basal keratinocyte localization in hyperplastic skin diseases and in benign tumors of the epidermis and that they are strongly expressed in basal cell carcinomas. In contrast, alpha 10.1.2 expression is decreased in keratinocytes that differentiate in vitro and is lost in epidermal dysplastic conditions, in the invading front of squamous cell carcinomas of the epidermis, in microinvasive cervical cancers, and in well-differentiated squamous lung tumors. These findings indicate that alpha 10.1.2 beta 1 integrin is downregulated during keratinocyte differentiation in vitro and in vivo. Moreover, lack of alpha 10.1.2 expression in basal cells of squamous epithelia is associated with early dysplastic changes and with the acquisition of invasive capacity.

Antibodies, Monoclonal↗

PubMed1994

Keratinocyte transglutaminase expression varies in squamous cell carcinomas.

Type I transglutaminase (TGase I, keratinocyte or particulate transglutaminase) is a 92-kilodalton (kDa) protein expressed in abundance in cultured keratinocytes and in the hyperproliferative skin disorder psoriasis. To determine the expression of TGase I protein and mRNA, we studied tissue and established squamous carcinoma lines derived from different sources. Immunohistochemistry and Western blotting were used to detect TGase I protein with the B.C1 mouse monoclonal antibody. Only well-differentiated, skin-derived squamous carcinomas stained for TGase I. However, a precocious pattern of expression was seen overlying less-differentiated tumors. Compared to cultured human keratinocytes, squamous cell carcinoma (SCC) had many times less to 7.8 times more TGase I protein, greatest in the two most differentiated tumor lines 14-83 and ME-180. TGase I mRNA levels ranged from 0.010 to 0.00004 pg/microgram total RNA by reverse transcriptase-polymerase chain reaction using an internal standard. Protein expression correlated with mRNA levels in most SCC lines. When a human TGase I promoter was isolated and used to study genomic DNA, SCC1-83 was shown to have unique restriction enzyme fragments, including one indicative of methylation differences, also present within DNA from the KB line. These studies suggest that transcriptional control of TGase I gene expression in squamous carcinomas may be influenced both by cis elements in the promoter and by the degree of tumor squamous differentiation.

Alleles↗

PubMed1976

Ultraviolet light carcinogenesis in hairless mice: cell kinetics during induction and progression of squamous cell carcinoma as estimated by the double-labeling method.

The double-labeling method for studying cell cycle kinetics was applied to uninvolved epidermis of hairless mice (irradiated and unirradiated), and at various stages of ultraviolet light (UVL)-induced squamous cell carcinoma. The growth fraction (GF) was determined by continuous labeling with tritiated thymidine (3HTdR). The data indicate that the double-labeling technique is an acceptable method for studying cell kinetics in UVL-induced squamous cell carcinoma. The GF in normal epidermis (unirradiated and irradiated), hyperplastic epidermis, and lesions of squamous cell carcinoma is 1. The duration of cell generation (Tc) and DNA synthesis (Ts) periods decreased progressively with induction and progression of squamous cell carcinoma. For normal epidermis (irradiated mice) the Tc and Ts were 91 and 6.3 hr, respectively. In the hyperplastic epidermis, the Tc and Ts were reduced to 44 and 4.5 hr, respectively, while even lower values were obtained for the tumor (Tc = 16 hr, Ts = 3.1 hr). The labeling index (LI) in normal epidermis was 7% and increased progressively in hyperplastic epidermis (10%) and squamous cell carcinoma (19%). Epidermal cell differentiation in hyperplastic and tumor tissues appears to have been delayed (GF = 1), since cells above the basal layer, which in normal epidermis keratinize, retain the ability to proliferate, as evidenced by extensive incorporation of [3H]TdR in these cells. The results suggest that tumor production is associated with a progressive shortening of the cell cycle and delayed keratinization of epidermal cells.

Animals↗

PubMed2026

Lung Squamous Cell Carcinoma Harbouring a Novel PAX8::PPARγ Fusion and a FGFR2 Exon 7 Missense Mutation.

Comprehensive molecular profiling is now routinely performed in newly diagnosed non-small cell lung carcinomas (NSCLCs) to identify actionable genomic alterations. Although numerous molecular abnormalities have been described in lung carcinomas, rare and unexpected gene fusions may create significant diagnostic challenges, particularly when they are characteristically associated with tumours of different lineages. To our knowledge, this is the first reported case of a primary lung squamous cell carcinoma harbouring an in-frame PAX8::PPARγ fusion with a concurrent FGFR2 exon 7 missense mutation (p.W290C). An 80-year-old man with a smoking history exceeding 50 years presented with a rapidly enlarging PET-avid right upper lobe pulmonary mass. Bronchial brushing cytology demonstrated a hypercellular malignant neoplasm composed of pleomorphic squamoid cells with hyperchromatic nuclei, dense cytoplasm and extensive necrosis. Cell block material showed squamous morphology and diffuse p40 positivity, supporting squamous differentiation. Reflex next-generation sequencing identified an FGFR2 exon 7 missense mutation (p.W290C; c.870G>C) and targeted RNA fusion analysis demonstrated an in-frame PAX8::PPARγ fusion resulting from a t(2;3)(q13;p25.2) translocation. Because PAX8::PPARγ rearrangements are strongly associated with follicular thyroid neoplasms, extensive clinicoradiologic and immunohistochemical correlation was performed to exclude metastatic thyroid carcinoma. Imaging studies showed no thyroid lesion or residual thyroid tissue, and tumour cells were negative for thyroglobulin, TTF-1 and PAX8. Correlation of the clinical history, radiologic findings, cytomorphology, immunophenotype and molecular profile supported the diagnosis of primary lung squamous cell carcinoma. This case expands the molecular spectrum of lung squamous cell carcinoma and highlights the importance of integrated cytopathologic, immunohistochemical, molecular and radiologic evaluation when unexpected gene fusions are identified in cytology specimens.

FGFR2 exon 7 missense mutation↗

PubMed1997

Epidermal differentiation and squamous metaplasia: from stem cell to cell death.

Epidermal differentiation is a multi-step process defined by a cascade of interrelated changes in the expression of growth-regulatory and differentiation-specific genes (Fig. 1). Irreversible growth arrest is an early event in epidermal differentiation which occurs when cells transit from the basal to the innermost suprabasal layer of the skin and begin to express squamous-specific genes. In culture, interferon gamma, phorbol esters, confluence and growth in suspension are effective signals to induce irreversible growth arrest and differentiation. The induction of differentiation-specific genes occurs either concomitantly with or following growth arrest and is believed to be linked to the molecular events that control irreversible growth arrest. Such a link has been demonstrated in other cell systems undergoing terminal differentiation, such as myogenesis and adipogenesis. Genes encoding proteins involved in the formation of the cross-linked envelope are one set of squamous-specific genes which are induced in the suprabasal layers and include transglutaminase I and III, involucrin, loricrin and cornifins/small proline-rich proteins. Squamous-specific genes exhibit not only different patterns of tissue-specific expression but are also induced at different stages during differentiation, suggesting that transcription of individual genes is regulated by distinct mechanisms. The latter is supported by the identification of different sets of regulatory elements controlling the transcription of these genes. The importance of understanding both the mechanisms that regulate growth arrest and the differentiation program is emphasized by the association found between specific skin diseases and genetic alterations in growth-regulatory genes as well as differentiation markers. In addition, studies into those mechanisms will provide insight into the control of squamous metaplasia and the development of squamous cell carcinomas.

Amino Acid Sequence↗

PubMed1997

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions.

This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (> 10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.

Adenocarcinoma↗