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Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential.

The acquisition of an invasive or metastatic phenotype in malignant neoplasms is often correlated with reduced cellular adhesiveness. We investigated the expression of the adhesion-associated cytoplasmic protein, vinculin, in normal and neoplastic human squamous epithelia, as well as in metastases of squamous cell carcinomas, and correlated the results with invasiveness and metastatic potential. Tissue samples from various tumors were examined, including basal cell carcinomas (BCC), keratoacanthomas, and squamous cell carcinomas (SCC). In addition, lymph node metastases from nine of the SCC were tested in this study. Our results indicate that most BCC, keratoacanthomas, and in situ SCC display strong positive staining for vinculin. The level of immunolabeling for vinculin and its pattern of distribution in the low malignant, nonmetastasizing lesions was similar to those observed in normal squamous epithelia. In contrast, in SCC, which are invasive and possess metastatic potential, as well as in their metastases, vinculin labeling was negative or poor, irrespective of their degree of differentiation. In conclusion, poor vinculin labeling in tumors of squamous epithelial origin examined here appears to be related to the metastatic potential of the tumor. Vinculin immunostaining of primary tumors originating in stratified squamous epithelia may thus be of value in helping to determine the metastatic potential of these neoplasms.

Basal Cell Carcinoma↗

Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study.

BACKGROUND: Immunosuppressive treatments have been associated with an increased risk of skin cancer, especially in patients who have had organ transplants. We aimed to assess the risk of skin cancer in patients taking the ciclosporin who had been exposed to psoralen and ultraviolet-A light (PUVA) and other treatments for severe psoriasis. METHODS: We did a nested cohort crossover study of 28 participants in the PUVA follow-up study who were on ciclosporin to compare the frequency of squamous-cell carcinoma before and after first use of ciclosporin. We also analysed the entire PUVA study cohort (1380) to assess the relation between use of this drug and frequency of squamous-cell carcinoma. FINDINGS: In the 5 years before first use, six of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell carcinomas. In the nested cohort, after adjustment for amount of exposure to PUVA and methotrexate, incidence of tumours was seven times higher after first ciclosporin use than in the previous 5 years (incidence rate ratio 6.9 [95% CI 4.3-11]). Multivariate analysis of the entire cohort showed that risk of squamous-cell carcinoma after any use of ciclosporin is close to that recorded for at least 200 PUVA treatments (3.1 [2.6-3.7] and 2.8 [2.6-3.2], respectively). INTERPRETATION: The risk of squamous cell cancer of the skin is increased by ciclosporin in patients with psoriasis who have been exposed to PUVA. Such risks should be balanced against the effectiveness of the drug and possible newer immunosuppressive agents.

Carcinoma, Squamous Cell↗

Molecular cloning of human squamous cell carcinoma antigen 1 gene and characterization of its promoter.

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2, which are 95% identical in nucleotide sequence. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. We analyzed here the sequence and the promoter activity of the 5'-flanking region of the SCCA1 gene. Deletion analysis of SCCA1 and SCCA2 promoter identified a 471-bp core promoter region upstream of the transcription start site. The transcriptional activity of SCCA1 promoter was up-regulated in squamous cell carcinoma cells, compared with keratinocyte and adenocarcinoma cells. The ratios of SCCA1 to SCCA2 promoter activity in squamous cell carcinoma, keratinocyte and adenocarcinoma cells were respectively 1.6, 5.3 and 2.8. Position -50 of SCCA1 and SCCA2 promoters played an important role in determining the promoter activities of SCCA1 and SCCA2. These findings suggest that the transcriptional regulation of SCCA1 and SCCA2 might differ among squamous cell carcinoma, keratinocyte and adenocarcinoma cells, and that SCCA1 promoter might be a potential target of gene therapy for squamous cell carcinoma.

Antigens, Neoplasm↗

Prognostic significance of thrombomodulin expression and vascular invasion in stage I squamous cell carcinoma of the lung.

Thrombomodulin (TM) is an important modulator of intravascular coagulation. TM exists on endothelial cells and on several types of tumor cells, especially squamous cell carcinoma cells. Tumor cell TM is thought to be associated with progression and metastasis of the tumor. To evaluate the prognostic significance of TM in lung cancer, we examined TM expression and vascular invasion in surgical specimens obtained from 90 patients with completely resected stage I non-small cell lung cancer (NSCLC). In addition, we correlate these pathologic data to other clinicopathologic data, including the outcome of the patients. Squamous cell carcinomas had a significantly higher incidence (P<0.0001) of TM expression (22/36 cases, 61%) than adenocarcinomas (9/54 cases, 17%). In 36 squamous cell carcinoma patients, both vascular invasion (P=0.0153; risk ratio 6.507) and TM non-expression (P=0.0282; risk ratio 3.584) were significant for a poor prognosis. Univariate analysis of patient survival rates also revealed that vascular invasion and TM expression were significant prognostic factors (P=0.0036 and 0.012, respectively). Further, combination analysis of vascular invasion and TM expression in the squamous cell carcinoma patients showed that the 5-year survival rate was 90% in patients with TM expression and without vascular invasion, but 21% in patients with vascular invasion and without TM expression (P=0.0004). Since our results suggest that vascular invasion and TM expression are independent prognostic factors of stage I squamous cell carcinoma of the lung, and since the two factors play different roles in the metastatic process of cancers (promotion of metastasis by vascular invasion and inhibition of metastasis by TM expression), the combination evaluation of vascular invasion and TM expression may be very significant in evaluating the prognosis of patients with completely resected stage I squamous cell carcinoma.

Adult↗

Expression of caveolin-1 is associated with poor prognosis of patients with squamous cell carcinoma of the lung.

BACKGROUND: Caveolin-1, as a major component of caveolae, is involved in the regulation of cell cycle by impacting various signaling pathways. Previous studies of caveolin-1 in cancer showed two contrary results. In most in vitro studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the elevated expression of caveolin-1 was often reported to be associated with poor clinical outcome in human studies. These results indicate differential biological functions of caveolin-1 depending on the development and progression stage of cancer in vivo. METHODS: To clarify the correlation between the clinicopathologic profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1, 107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous cell carcinomas were immunohistochemically evaluated for the expression of caveolin-1 by the tissue-array method. RESULTS: Caveolin-1 was expressed in 34 cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The expression of caveolin-1 was statistically correlated with pathologic stage (stage I and II vs. III; P<0.001), pT (T1 and T2 vs. T3 and T4; P=0.001), and pN (N1 vs. N2 and N3; P=0.0143). The patients with caveolin-1 expression in pulmonary squamous cell carcinomas showed a poorer prognosis than those in caveolin-1-negative group (P=0.0345). CONCLUSION: The expression of caveolin-1 is significantly correlated with advanced pathologic stage and poor prognosis in pulmonary squamous cell carcinoma. The results of current study suggest that the expression level of caveolin-1 may be a candidate factor for predicting prognosis in patients with pulmonary squamous cell carcinoma.

Adult↗

A small proline-rich protein, spr1: specific marker for squamous lung carcinoma.

We have identified a small proline-rich protein, spr1, which is a sensitive and specific marker for distinguishing squamous cancer from the other cell types of lung carcinoma. A rabbit antiserum against a 15-amino-acid peptide of the C-terminus of spr1 was prepared. The specificity of this antiserum was demonstrated in normal squamous tissues by Western blotting and immunohistochemical analysis. Expression of spr1 in 63 cases of formalin-fixed and paraffin-embedded human bronchogenic carcinoma was studied by immunohistochemical staining. For these 63 cases of bronchogenic carcinoma previously diagnosed by hematoxylin/eosin (H/E) staining, the number of spr1-positive cases/total number of H/E cases of each cell type of lung cancer were as follows: 20/20 of squamous carcinoma, 2/18 of adenocarcinoma, 4/14 of large-cell carcinoma, and 0/11 of small-cell lung carcinoma. Squamous differentiation evidenced by spr1 expression was substantiated by the presence of squamous features observed under transmission electron microscopy (TEM). We conclude that spr1 is a sensitive and specific marker for squamous bronchogenic carcinoma.

Biomarkers, Tumor↗

Keratoacanthoma and squamous cell carcinoma of the skin: immunohistochemical localization of involucrin and keratin proteins.

Fifteen keratoacanthomas and fifteen squamous cell carcinomas of the skin were examined by immunoperoxidase methods for involucrin and both 45- and 63-kilodalton keratins. Keratoacanthomas showed a relatively homogeneous staining pattern for involucrin; all cells except basal cells stained with mild to moderate intensity. Squamous cell carcinomas disclosed a highly irregular involucrin staining pattern with marked variation in staining intensity from cell to cell. Staining patterns for keratin proteins did not appear to distinguish between keratoacanthomas and squamous cell carcinomas. The 45-kilodalton keratin pattern showed diffuse staining within both keratoacanthomas and squamous cell carcinomas, and the 63-kilodalton keratin pattern consisted of focal staining, mostly of dyskeratotic cells. These results suggest that involucrin may serve as a diagnostic aid in differentiating between squamous cell carcinomas and keratoacanthomas. In addition, other lesions in the differential diagnosis of keratoacanthoma and squamous cell carcinoma were also examined for involucrin.

Adult↗

Human papillomavirus and oesophageal squamous cell carcinoma in the UK.

Human papillomavirus (HPV) has previously been identified in up to 67% of squamous cell carcinomas of the oesophagus. In particular, HPV types of 16 and 18 are believed to play an important role in neoplastic transformation, by means of their oncoproteins E6 and E7. Most of these studies, however, pertain to areas of high incidence of squamous cell carcinoma of the oesophagus (the Far East and South Africa). It is not known if HPV plays any role in the development of oesophageal squamous cell carcinoma in the UK, where the tumour is relatively uncommon. The polymerase chain reaction was used to examine frozen tissue from 22 oesophageal squamous cell carcinomas for the presence of specific DNA sequences from oncogenic strains of HPV. PCR products were further analysed by Southern blot hybridization. No HPV sequences were detected in any tumours. These results suggest that these types of HPV are not associated with oesophageal squamous cell carcinoma in this country. It is unlikely, therefore, that HPV plays a significant role in the pathogenesis of squamous cell carcinoma of the oesophagus in the UK.

Adult↗

Cytokeratin expression in squamous cell carcinoma of the lung and oral cavity: an immunohistochemical study with possible clinical relevance.

OBJECTIVE: Serologic identification of the fragment of cytokeratin 19 known as CYFRA 21-1 has been used for early detection of squamous cell carcinoma of the lung. The sensitivity of the CYFRA 21-1 assay in detecting oral cancers is lower than that in detecting lung cancers. To clarify the reason for this, we compared the cytokeratin expression in these cancers, with special reference to cytokeratin 19. STUDY DESIGN: Oral squamous cell carcinomas and lung squamous cell carcinomas were immunostained with cytokeratin 19, cytokeratin 10, and cytokeratin 13 antibodies. Staining intensity was scored on a graduated scale from 0 to 4. RESULTS: With respect to cytokeratin 19, the stainings of all lung cancers were scored as 4, which indicates a greater expression of cytokeratin 19 than is seen in oral cancers (p < 0.01). With an average cytokeratin 19 staining score of 1.67, oral cancers ranked lowest among the antibodies. Squamous cell carcinomas of the maxillary sinus arising from pseudostratified ciliated epithelium were highly expressive of cytokeratin 19. A marker for keratinizing cells (cytokeratin 10) and a marker for squamous cells (cytokeratin 13) were expressed more frequently and intensely in oral cancers (p < 0.01) than in lung cancers (p = 0.019). CONCLUSIONS: From the viewpoint of immunohistochemistry, cytokeratin 19 was found to be a tumor marker with low specificity and sensitivity in oral cancers. The staining results suggested that poor expression of cytokeratin 19 by oral squamous cell carcinoma may result in a low serum value of CYFRA 21-1 in patients with this condition.

Antibodies↗

Squamous and/or glandular differentiation in urothelial carcinoma: prevalence and significance in transurethral resections of the bladder.

BACKGROUND: It is controversial if urothelial carcinoma of the bladder with squamous and/or glandular differentiation is a more aggressive neoplasm than conventional urothelial carcinoma. DESIGN: A total of 165 transurethral resections of the bladder were reviewed. A group with squamous and/or glandular differentiation was compared to a group without this finding. The chi-square test was used to assess the association of the groups with stage (TNM, 1997). RESULTS: Of the total of 165 transurethral resections of the bladder, 153 (92.72%) were conventional urothelial carcinomas and 12 (7.27%) showed squamous and/or glandular differentiation. The distribution according to stage was 84 (54.9%), 35 (22.9%) and 34 (22.2%) for the group without differentiation and 0 (0%), 3 (25%) and 9 (75%) for the group with squamous and/or glandular differentiation, respectively for stages pTa, pT1 and pT2. Tumors with squamous and/or glandular differentiation showed a significant statistical correlation to higher stage at clinical presentation (p < 0.0001). There was no significant statistical relation according to age (p = 0.8433), sex (p = 0.5672) or race (p = 0.3137). CONCLUSIONS: The results suggest that urothelial bladder carcinomas with squamous and/or glandular differentiation are more aggressive neoplasms. There was a significant statistical correlation between tumors with this differentiation and higher stage at clinical presentation.

Carcinoma, Squamous Cell↗

CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients.

CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or >/=5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27(Kip1) and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.

Adenocarcinoma↗

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma.

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms. Archival, routinely processed slides were subjected to citrate-based antigen retrieval, exposure to anti-p63 monoclonal 4A4, and developed with a streptavidin-biotin kit and diaminobenzidine as chromogen. p63 was detected in 100% of the adenoid cystic carcinomas (n=14) and 100% of basaloid squamous cell carcinomas (n=16). Basaloid squamous cell carcinomas consistently displayed diffuse p63 positivity, with staining of nearly 100% of tumor cells. In contrast, adenoid cystic carcinoma displayed a consistently compartmentalized pattern within tumor nests. Compartmentalization was manifested in two patterns: (1) selective staining of a single peripheral layer of p63-positive cells surrounding centrally located tumor cells that were p63-negative and (2) tumor nests consisting of multiple contiguous glandular/cribriform-like units of p63-positive cells surrounding or interspersed with p63-negative cells. p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. p63 positivity in adenoid cystic carcinoma appears to be homologous to that seen in the basal and/or myoepithelial compartments of salivary gland and other epithelia, and may signify a stem-cell-like role for these peripheral cells. Diffuse p63 positivity in basaloid squamous cell carcinoma suggests dysregulation of p63-positive stem cells in poorly differentiated squamous carcinoma.

Carcinoma, Adenoid Cystic↗

TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material.

In histology and cell block sections, antibodies to thyroid transcription factor-1 (TTF-1) and p63 have been demonstrated to be useful markers for distinguishing between small-cell lung carcinoma and poorly differentiated pulmonary squamous cell carcinoma. In this study, we assessed the utility of TTF-1 and p63, as an antibody panel, for differentiating between these two neoplasms in previously Papanicolaou (Pap)-stained cytologic smears and cytospin slides. Twenty-six lung carcinomas (13 small-cell lung carcinomas, 13 poorly differentiated pulmonary squamous cell carcinomas) were evaluated. One or two previously 95% ethanol-fixed, Pap-stained smears or cytospin slides were selected from each case. The cytologic material from these slides was transferred to positively charged slides. Unstained recuts were obtained from the corresponding histologic specimens or cell blocks. Immunohistochemical staining for TTF-1 and p63 was performed on the paired samples from each tumor. All (13/13) small-cell lung carcinomas were negative for p63 and 92% (12/13) were positive for TTF-1. Conversely, all (13/13) poorly differentiated pulmonary squamous cell carcinomas expressed p63 and did not express TTF-1. Immunoreactivity for p63 was also noted in bronchial reserve cells and metaplastic squamous cells. The immunostaining results obtained from the cytology slides were concordant with those of the histology or cell block sections in all cases. The results of this study show that TTF-1 and p63 immunostaining can be successfully applied to previously Pap-stained cytologic material, as an antibody panel, to facilitate pathologic differentiation between small-cell lung carcinomas and poorly differentiated pulmonary squamous cell carcinomas. p63 immunostaining, however, must be interpreted in conjunction with cytomorphology to distinguish between poorly differentiated pulmonary squamous cell carcinomas and benign cellular constituents of the lung.

Adult↗

Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis.

While most cancers of the uterine cervix are squamous cell carcinomas, the relative and absolute incidence of adenocarcinoma of the uterine cervix has risen in recent years. It is not clear to what extent risk factors identified for squamous cell carcinoma of the cervix are shared by cervical adenocarcinomas. We used data from six case-control studies to compare directly risk factors for cervical adenocarcinoma (910 cases) and squamous cell carcinoma (5649 cases) in a published data meta-analysis. The summary odds ratios and tests for differences between these summaries for the two histological types were estimated using empirically weighted least squares. A higher lifetime number of sexual partners, earlier age at first intercourse, higher parity and long duration of oral contraceptive use were risk factors for both histological types. Current smoking was associated with a significantly increased risk of squamous cell carcinoma, with a summary odds ratio of 1.47 (95% confidence interval: 1.15-1.88), but not of adenocarcinoma (summary odds ratio=0.82 (0.60-1.11); test for heterogeneity between squamous cell and adenocarcinoma for current smoking: P=0.001). The results of this meta-analysis of published data suggest that squamous cell and adenocarcinomas of the uterine cervix, while sharing many risk factors, may differ in relation to smoking. Further evidence is needed to confirm this in view of the limited data available.

Adenocarcinoma↗

Decreased growth inhibitory responses of squamous carcinoma cells to interferon-gamma involve failure to recruit cki proteins into cdk2 complexes.

Interferon-gamma induces an irreversible growth arrest and squamous differentiation in normal human epidermal keratinocytes. We present for the first time a careful biochemical analysis of the cell-cycle-related events that occur during interferon-gamma treatment of normal human epidermal keratinocytes. The interferon-gamma-induced irreversible growth arrest state is characterized by inhibition of cyclin-dependent kinases, prevention of Rb and p130 (Rb2) phosphorylation, and increases in p27(Kip1), p16(Ink4a), and p130 proteins, together with a transient increase in p21(Waf1/Cip1). Cells derived from squamous cell carcinomas are less responsive to interferon-gamma and do not terminally differentiate. We exploited these differences in response to interferon-gamma in order to identify the particular molecular defects in cell cycle control that promote carcinogenesis in squamous epithelia. In several squamous cell carcinoma cell lines as well as in interferon-gamma-insensitive HaCaT cells, interferon gamma was unable to significantly induce levels of p130 and/or p16 protein. In addition, p21 association with cdk2 complexes was undetectable in either the absence or the presence of interferon-gamma and, unlike normal human epidermal keratinocytes, p27 association with cdk2 did not increase with interferon-gamma treatment. These multiple defects appear to be intrinsic to the mechanisms of cell cycle regulation rather than due to defects in the interferon-gamma signaling pathway, as induction of several interferon-gamma-responsive genes including Stat 1, IRF-1, and p21 itself was normal. Interestingly, exogenous expression of p21 protein in the squamous cell carcinoma cell lines by adenovirus carrying wildtype p53 or p21 cDNA cooperated with interferon-gamma to produce a greater inhibition of growth than either agent alone, even though p21 protein could barely be detected in cdk2 complexes. We conclude that squamous cell carcinoma cells have intrinsic defects in their ability to regulate cdk-cki complexes in response to differentiation signals.

CDC2-CDC28 Kinases↗

Carcinosarcoma of the oesophagus showing neuroendocrine, squamous and glandular differentiation.

AIM: A case of oesophageal carcinosarcoma occurring in a previously fit, 64-year-old man is reported. CASE SUMMARY: The carcinomatous component displayed neuroendocrine, squamous and glandular differentiation: the sarcomatous component showed no specific features of differentiation. In-situ squamous carcinoma was present in the adjacent squamous mucosa. The most superficial part of invasive tumour consisted of carcinosarcoma with a predominant neuroendocrine epithelial component. Squamous carcinoma without an accompanying sarcomatous component occupied most of the deeper part of the tumour, suggesting outgrowth of this tumour type by a selective growth advantage. CONCLUSION: We speculate that further tumour growth might have led to complete replacement of the tumour by pure squamous carcinoma, and that other advanced oesophageal squamous carcinomas might have had their origin in a short-lived carcinosarcomatous phase.

Adenocarcinoma↗

Primary squamous cell carcinoma of the thyroid gland: an entity with aggressive clinical behaviour and distinctive cytokeratin expression profiles.

AIMS: Primary squamous cell carcinoma of the thyroid gland is uncommon. This study aims to identify the clinicopathological features and the pattern of expression of cytokeratins and oncoproteins in this tumour. METHODS AND RESULTS: Histological slides from Chinese patients with thyroid cancer treated in our institution from 1980 to 1999 were reviewed. Patients with primary squamous cell carcinoma of the thyroid were identified and their clinical records were analysed. The expression of cytokeratins (CKs), p53 and p21 in these cases were also studied by an immunohistochemical method. Four women (mean age 71 years) with squamous cell carcinoma of thyroid were found. The main presenting features were signs and symptoms of airway obstruction in three patients and neck swelling in one. The tumours were located at the right lobe (n=2), left lobe (n=1) or in both lobes of the thyroid (n=1). One patient died shortly after admission and the other three died within 4 months after thyroidectomy. The p53 protein was positive in 50% (2/4) of the tumours and p53+ tumours were poorly differentiated. The tumours were negative for p21. CK19 was expressed in all the tumours while CK7 expression was noted in 3/4 of the tumours. One carcinoma showed focal positivity to CK18. The tumours were negative for CKs 1, 4, 6, 10/13 and 20. The pattern of cytokeratin expression in squamous cell carcinoma of the thyroid gland was different from carcinoma showing thymus-like differentiation (CASTLE) of the thyroid gland and oesophageal squamous cell carcinoma. CONCLUSIONS: Squamous cell carcinoma of the thyroid has aggressive clinical behaviour and characteristic CK expression pattern. p53 over-expression in these tumours was associated with tumour differentiation.

Aged↗

[Lichen sclerosus and squamous cell carcinoma of the vulva].

Genital lichen sclerosus in women is a clinically and histologically well defined disease. In addition to the classical atrophic form, there is a hypertrophic variant, which is characterised histologically by squamous cell hyperplasia. The aetiology is unknown but an autoimmune pathogenesis seems most likely. Infectious or hormonal influences do not play a major role. We describe a squamous cell carcinoma of the vulva with a co-existing lichen sclerosus. This case raises again the question of a precancerous potential of lichen sclerosus. In the dermatological literature, only a few cases with association of lichen sclerosus and squamous cell carcinoma are known. This is in contrast to gynaecological literature, where a high number of squamous cell carcinomas has been described. Gynaecologists search for the histological findings of lichen sclerosus adjacent to squamous cell carcinoma. Such an attempt is not valid without the clinical signs of lichen sclerosus, so that indeed classical lichen sclerosus does not seem to be a precancerous lesion. On the other hand, the hypertrophic form of lichen sclerosus seems to be associated with squamous cell carcinoma in about 3-5% of case.

Aged↗