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Background: The development of cervical carcinoma is influenced by multiple factors, including the presence of certain high risk types of human papillomavirus. The purpose of the current study was to investigate possible cooperating genetic changes by examining the expression of p53, p62 myc, and p21 ras in cervical biopsy specimens., Methods: Three hundred and ninety-five cervical biopsy specimens representing normal through high grade cervical intraepithelial neoplasia (CIN) were screened by immunohistochemistry for expression of p53, p62myc, and p21ras., Results: Neither the proportion of tissues staining positive for a given protein nor the staining patterns within the epithelial layers differed significantly among normal or CIN biopsy samples. However, grade specific nuclear staining of p21ras was found in the cells of 10 lesions that were classified as CIN I by histology., Conclusions: These results established the normal distribution and expression patterns of p53, p62myc, and p21ras within 395 cervical biopsy samples representing normal through CIN III histology. The expression of these proteins (e.g., staining intensity and layer of epithelium staining positive) is similar in normal tissues and those demonstrating all grades of CIN.

Background: The authors previously described a large pedigree with familial gastric polyposis and a high incidence of gastric cancer and demonstrated the autosomal dominant pattern of inheritance. The current study described the histologic and immunohistologic features of the lesions in an attempt to clarify the mechanisms underlying gastric carcinogenesis in this family., Methods: The authors studied the histopathologic and histochemical features of several gastric specimens of nine members of this family and searched for the expression of carcinoembryonic antigen (CEA), p21 protein (ras oncogene), p53 protein (p53 suppressor gene), and simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, and T antigen before and after neuraminidase) and for the presence of Helicobacter pylori., Results: The two carcinomas available for histologic revision were of the diffuse type. One of them apparently originated from a hyperplastic polyp. Hyperplastic polyps were diagnosed in five of seven patients without carcinoma. The remaining two patients had marked foveolar hyperplasia. Chronic atrophic gastritis with complete intestinal metaplasia (IM) was seen in three patients. p53 protein was not expressed in any of the cases. CEA and ras p21 oncoprotein were found in six and eight cases, respectively (mainly in hyperplastic foveolar epithelium). Tn, sialosyl-Tn, and T antigen were expressed in every case. H. pylori colonization was detected in all but the two patients with carcinoma., Conclusions: The authors concluded that foveolar hyperplasia/hyperplastic polyps play a key role in the development of diffuse carcinoma in this inherited polyposis, confined to the stomach, with hyperplastic phenotype. The genetic and environmental mechanisms underlying this particular situation remain to be clarified.

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A (P less than 0.05), O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P less than 0.05), the pathologic grade and stage (P = 0.002), and the tumor DNA ploidy (P less than 0.05). Smoking status correlated aneuploidy (P less than 0.05) and tumor expression of ORP-p21 (P less than 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer.

The clinical significance of ras oncogene expression in non-small cell lung cancer was evaluated in 116 surgically treated patients. Archival paraffin sections of the tumors were analyzed immunohistochemically using anti-ras p21 monoclonal antibody (MoAb) rp-35, and p21 staining was correlated with clinicopathologic parameters and survival. Positive reactions (+ and ++) were observed in 72.5% of the adenocarcinomas and 55.6% of the squamous cell carcinomas studied. The T1 tumors showed a ++ reaction less frequently than T2 and T3 tumors (P less than 0.05). Stage I tumors also were less reactive with MoAb rp-35 than tumors in more advanced stages (P less than 0.05). Survival analysis showed that patients with p21-negative tumors had significantly longer survival times (a 5-year survival rate of 64.1%) than those with p21 + tumors (38.0%, P less than 0.05) or those with p21 ++ tumors (11.5%, P less than 0.005). The significant correlation between p21 staining and patient survival was independent of histologic type, stage of disease, tumor or node status, and the resectability of tumors. On Cox's multivariate analysis, p21 staining was a major and independent prognostic determinant of survival. These results suggest that enhanced ras p21 expression may be one of the important biologic and clinical markers indicating the malignant potential of non-small cell lung cancer.

To evaluate biologic characteristics of neuroblastoma, the authors examined the expression of Ha-ras gene (Ha-ras p21) in 103 primary tumors obtained at the time of diagnosis. Higher expression of the Ha-ras p21 in tumor cells showed a significant association with lower clinical stage of the tumor at diagnosis (chi-square = 35.418, degrees of freedom [df] = 9, P less than 0.001) and survival of the patients (chi-square = 37.111, df = 3, P less than 0.001). Thirty-six (84%) of 43 patients with decreased Ha-ras p21 expression died of aggressive disease. The Ha-ras DNA was examined in the 32 tumors by Southern blot analysis. Neither augmentation nor deletion of the Ha-ras DNA was observed. Amplification of the N-myc DNA was also examined in 43 cases in comparison with Ha-ras p21 expression. N-myc amplification was detected in 12 (55%) of 22 patients who died, and 19 (86%) of the 22 patients showed a low expression of the Ha-ras p21 in tumor cells. Eighteen (86%) of 21 survivors showed a high expression of the Ha-ras p21. The expression of Ha-ras p21 was thought to be a clinically important marker for prognosis in children with neuroblastoma.

To examine the correlations between ras oncogene expression and the development of cervical cancer, the authors studied the reactivity of cervical intraepithelial neoplasia (CIN) and microinvasive lesions of the human uterine cervix by using anti-ras p21 mouse monoclonal antibody rp35. The frequency of positive p21 staining increased with increased grades of malignancy from 17.9% in CIN 1 to 28.9% in CIN 2 and 53.9% in CIN 3, whereas in microinvasive carcinoma it was 50.0%. Furthermore, ten cases of lesions that regressed during a 1-year follow-up period were positive for ras p21 in 20% of cases, but 14 cases of lesions that progressed and developed into higher graded lesions during the 2- to 5-year follow-up period had a 50.0% rate of positive p21 staining. It was concluded that ras oncogene product p21 correlates with the early phase of carcinogenesis of squamous cells of the uterine cervix.

The chromosomal banding pattern and the in vitro growth characteristics of a metastatic epithelioid sarcoma are described. The cultured tumor cells retained growth characteristics as well as ultrastructural and immunohistochemical properties similar to the cells of the primary tumor. Cytogenetic analysis revealed a modal range in the diploid-hypodiploid region, a finding which was corroborated by quantitative DNA determinations of both the primary tumor and a lymph node metastasis. Fourteen different marker chromosomes were identified. The most frequent clonal rearrangement was a 1p-marker resulting from a short arm terminal deletion, i.e., del (1) (p21-22). A similar 1p- marker has previously been observed in an established epithelioid sarcoma cell line. The finding of an apparently identical 1p-marker in two of two analyzed epithelioid sarcomas suggests that this rearrangement may be a primary cytogenetic abnormality in epithelioid sarcoma. An elevated ras p21 expression was demonstrated using immunohistochemical methods. The possible involvement of the N-ras gene and/or a tumor suppressor in the 1p deletion is considered.