Serum squamous cell carcinoma antigen: a potential marker for benign vulval disease?

Benign vulval disease comprises a variety of disorders and can affect women of all ages. To date, the optimal management of these conditions has been uncertain and not subjected to a systemic prospective approach. It is recognized that benign vulval disease has a potential premalignant potential. Squamous cell carcinoma antigen (SCCA) has shown in different studies to be an effective means of monitoring the course of the disease in cervical carcinoma. Elevated levels of SCCA have been found in the skin. In addition, raised SCCA levels have been found in non-carcinomatous inflammatory dermatoses, and the levels observed correlated with the extent of the disease and the response to therapy. It was thought that SCCA might prove to be a useful marker for benign vulval disease, and in our pilot study the objectives were to determine if levels of SCCA are elevated in patients with that disease and to assess whether there is an association between SCCA and clinical response to treatment.     

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.     

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.     

Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia

In Okinawa, a subtropical island in southern Japan, squamous cell carcinoma (SCC), especially the well-differentiated form, is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patients with SCC from Okinawa, moreover, were positive for human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, in combination. On the other hand, less than 30% of the mainland patients were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a significant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component in these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged in size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia. In addition, aberrant expression of p53 was demonstrated in a large number of the SCC cases in Okinawa. The enlarged adenocarcinoma cells adjacent to the SCC components in adenosquamous carcinomas also showed aberrant expression of p53. The recent advances in the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied in general, classifying lung tumors into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histologic types, molecular genetic studies according to a more detailed histological subclassification is needed.     

CYFRA 21-1 is a useful marker for esophageal squamous cell carcinoma

BACKGROUND: CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC. METHODS: Expression and production of cytokeratin-19 in the authors' six established esophageal SCC cell lines were determined by immunocytochemical staining and enzyme-linked immunoadsorbent assay, respectively. The correlation between serum CYFRA 21-1 levels and expression of cytokeratin-19 in human tumors was investigated by immunohistochemical staining. The correlation between serum CYFRA 21-1 levels and clinicopathologic factors was examined in 48 patients with esophageal SCC, as were SCC antigen and carcinoembryonic antigen (CEA). RESULTS: Of the 6 cell lines, 5 lines expressed cytokeratin-19 in their cytoplasm and produced soluble cytokeratin-19 fragments. Twenty-three of 48 patients had elevated CYFRA 21-1 levels (>3.5 ng/mL), whereas none of the reference group (consisting of healthy volunteers or patients with benign disease) showed positive levels. The specificity, sensitivity, and accuracy of CYFRA 21-1 were 100%, 47.9%, and 66.7%, respectively. CYFRA 21-1 showed significantly higher sensitivity and accuracy than SCC antigen or CEA (P < 0.05). Univariate analysis revealed that CYFRA 21-1 levels correlated with disease progression (including tumor size, tumor depth, and pTNM stage), resectability, and curability. There was a significant association between the level of CYFRA 21-1 and its intensity of immunohistochemical staining in vitro as well as in vivo. CONCLUSIONS: CYFRA 21-1 appears to be a useful marker for human squamous cell carcinoma of the esophagus.     

Keratinizing desquamative squamous metaplasia of the kidney mimicking transitional cell carcinoma

A 54-year-old patient, who had a remote history of radial nephrotomy for nephrolithiasis, presented with a symptomatic renal mass. The lesion was suspicious for malignancy on excretory urography, retrograde pyelogram, and computed tomography. A nephroureterectomy was performed. The histologic sections showed keratinizing squamous metaplasia.     

Invasive squamous cell carcinoma of the cervix: is HLA-DQ a disease marker in Jewish patients?

HLA class I and class II were investigated in 30 Israeli patients with invasive squamous cell carcinoma of the cervix and compared to healthy controls. None of the studied serological specificities were found to be associated with the disease. Genomic DNA from the patients was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known DQA1 and DQB1 allelic variants. Fifteen out of the 30 patients tested (50%) were found to carry the DQA1*0501 allelic variant, which is common in the local healthy population (67%). DQB1*0302 was found in eight out of 30 patients (27%) while this allele was present in 17% of the healthy population, a difference which is not statistically significant. Our data indicate that there is no apparent association between invasive squamous cell carcinoma of the cervix and the HLA antigens and alleles studied including the alleles of the DQA and DQB loci in the Israeli population. Our findings indicate that MHC genes could not be useful in the diagnosis of squamous cell carcinoma of the cervix.     

Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract

PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.     

Assessing the patient at risk for oral squamous cell carcinoma

Patients and health care workers require continuing education to promote knowledge of the signs, symptoms, and risk factors for oral cancer. This paper reviews the literature assessing diagnostic tools that are currently available or being developed, in order to assist in the biopsy site selection and subsequent diagnosis of patients at risk for oral cancer. There is a general consensus that oral examination of patients at risk for oral squamous cell carcinoma (SCC) should be conducted on a routine basis. However, there can be false-positive and false-negative findings. Toluidine blue has been shown to be useful as an adjunct to the clinical examination when used by experienced clinicians. Exfoliative cytology is not currently used as a routine measure for the evaluation of lesions of the oral mucosa, but further development and the application of biologic markers to cytologic specimens may increase its value. Fluorescent imaging of malignant lesions of the oral mucosa has been shown to be sensitive and specific in animal models but thus far has been reported in only one human trial. The sensitivity and specificity of these techniques when used by general practitioners need to be assessed. Further, none of the above procedures has yet been shown to be a cost-effective public health measure in screening for oral cancer.     

Primary carcinoma of ureter with glandular metaplasia of transitional cell carcinoma: a case report

A case of primary mixed carcinoma of the right ureter in a 62-year-old woman is reported. Histopathology following a nephroureterectomy revealed well differentiated adenocarcinoma with a component of transitional cell carcinoma at the base of the tumor, suggesting glandular metaplasia of transitional cell carcinoma.     

A non-random deletion in the p53 gene in oral squamous cell carcinoma

In a retrospective study of the mutational spectrum of the p53 gene in oral squamous cell carcinoma, 80 primary tumours diagnosed in 1980-90 were included. Using polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis 47 mutations were found distributed in 39 of the tumours (49%). Unexpectedly, the majority of the mutations (29/47; 62%) were found in exon 8, and at sequencing 17 of them showed a 14 bp deletion in codons 287-292, causing formation of a stop codon and accordingly a truncated protein lacking the C-terminal. The majority of the patients with the 14 bp deletion were women (13/17), and it seemed as though certain potential risk factors for carcinoma of the head and neck were less common in this group.     

Demographic characteristics, pigmentary and cutaneous risk factors for squamous cell carcinoma of the skin: a case-control study

We conducted a case-control study of squamous cell carcinoma of the skin (SCC) in a cohort of people followed from 1987 to 1994. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age in 1987. On 2 occasions, in 1987 and 1992, dermatologists examined participants for skin cancers. Subjects were also asked on several occasions about skin cancers that they had had treated. Migrants to Australia had reduced risks of SCC. Furthermore, people who migrated to Australia early in life or, equivalently, lived in Australia for a long time had a higher risk than immigrants who arrived later in life or more recently. People who had southern European ancestry had a much lower risk of SCC than other subjects, most of whom were of British or northern European origin. Among Australian-born subjects of British or northern European ancestry, the skin's sensitivity to sunlight was strongly associated with SCC. The pigmentary traits of hair colour, eye colour and skin colour showed weaker associations. The degree of freckling on the arm was strongly predictive of risk. The risk of SCC increased strongly with increasing evidence of cutaneous solar damage and was most strongly associated with the number of solar keratoses. Our results show that sensitivity to sunlight and high levels of exposure to sunlight are important determinants of the risk of SCC.     

Mutations of the P53 tumor suppressor gene as clonal marker for multiple primary lung cancers

OBJECTIVES: Second primary lung cancers are prevalent after treatment for initial lung cancer, and the lung is also one of the most frequent sites for recurrence after removal of early-stage lung cancer. The objective of the present study is to clarify the clonal origin of the second tumor with the p53 gene mutation used as a clonal marker. METHODS: Of 794 consecutive patients who underwent pulmonary resection for primary lung cancer from 1980 to 1993, 22 required second pulmonary resection during the follow-up period, with a median interval of 38 months. We examined 16 of these patients for mutations of the p53 gene occurring in exons 5 through 8 by the polymerase chain reaction/single strand conformation polymorphism method. Differential diagnosis was also made on a morphologic basis, considering the degree of cellular differentiation and cytologic subtypes. RESULTS: Nine of the 16 patients analyzed had at least one p53 mutation in their tumors. We were thus able to make molecular diagnoses for these patients. The mutational status of the p53 gene was discordant in all nine patients, suggesting a different clonal origin despite the fact that six of them had almost identical histologic features. CONCLUSIONS: Analysis of p53 gene mutations was thus useful in distinguishing second primary lung cancers from recurrent tumors. The observed heterogeneity of p53 status was also in line with the "field cancerization" concept.     

Prognostic significance of p53 gene mutations in squamous cell carcinoma of the lung

The aim of the present study was to analyze the prevalence and clinical importance of p53 gene mutations in surgically treated squamous cell lung carcinoma. Sixty patients were included. Fifty-one patients in stages I to IIIa were submitted to radical resection. Twenty-five samples tested positive for the p53 immunohistochemistry assay, and were analyzed for p53 gene mutations. Eleven mutations were found. Patients harboring p53 gene mutations suffered a higher incidence of recurrence and a higher mortality rate. Disease-free interval and overall survival were shorter for patients with mutated p53 gene (p=0.03 and p=0.005, respectively).     

p53 expression in oral precancer as a marker for malignant potential

The potential of p53 protein expression as a marker for determining which oral precancerous lesions may transform to malignancy with time was assessed. We compared the p53 expression in archival formalin-fixed, paraffin-embedded tissues from 22 baseline biopsies of precancerous lesions that transformed to cancer in 4-25 years against that in 68 similar lesions that did not transform over the same time period. Twenty-nine percent of precancers that transformed were p53-positive at baseline, compared to 31% of the biopsies that did not transform to malignancy. When examined by immunohistochemical methods p53 expression failed to detect potential malignant status of oral precancer. Non-specificity of the assay may account for this result but overexpression of p53 due to DNA damage by tobacco/betel-quid in non-progressive lesions needs further study. Nine precancerous lesions became p53-immunoreactive from precancer to cancer. This may suggest p53 overexpression peaks close to the time of transition from precancer to cancer rather than early in the natural history of oral precancer.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Expression of P53 protein in laryngeal carcinoma and its clinical significance

Using the monoclonal antibody DO-7, the expressions of P53 protein in 38 cases of laryngeal squamous cell carcinoma (LSCC), and 29 cases of laryngeal benign neoplasms (LBN) were studied immunohistochemically. The results showed that: (1) 25 of 38 (66%) LSCCs, but only 2 of 29 (7%) LBNs showed expression of mutant-type P53 protein. The high rate of P53 protein expression was related to the occurrence of laryngeal carcinoma, and is valuable in diagnosis and differential diagnosis of laryngeal carcinoma; (2) in some LSCCs, the mutant-type P53 protein was also expressed in dysplastic epithelium near the cancer tissues. These epithelial cells near the tumor in which P53 gene has been altered, probably are the source or portent of tumor recurrence; (3) the five year survival rate of mutant-type P53 protein negative LSCC patients was higher than that of positive LSCC patients. The expression of mutant-type P53 protein might be related to LSCC prognosis.