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In this study, we examined the relationship between the histopathological grade and immunohistochemical localization of six genetically distinct type IV collagen α chains, the major component of basement membrane (BM), in normal and neoplastic colorectal tissues. In the normal colorectal mucosa, α1/α2(IV) and α5/α6(IV) chains were stained in all epithelial BM. However, α3/α4(IV) chains were restrictively immunostained in the BM of the apical surface epithelium. Similar immunostaining profiles for α1/α2(IV) and α5/α6(IV) chains were observed in tubular adenomas with mild/moderate atypia. However, in intramucosal carcinomas, both α1/α2(IV) chains were linearly stained in the BM of cancer cell nests, while the assembly of α5/α6(IV) chains into the BM was inhibited in a discontinuous or negatively stained pattern. The normal colorectal mucosa forms a second network of BM composed of α5/α6(IV), partly α3/α4(IV) chains, in addition to the classic network of α1/α2(IV) chains. The differential immunohistochemical localization of the type IV collagen α5/α6 chains could be one diagnostic marker for the invasiveness of colorectal cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our previous studies have demonstrated the significant role of brain-type glycogen phosphorylase (BGP) in the carcinogenesis of gastric carcinoma. The aims of the present study were to investigate the expression of BGP in colorectal carcinoma as well as the timing of this expression in the adenoma-carcinoma sequence (ACS), in comparison with the overexpression of p53 protein. We also sought to identify this marker in the particular colorectal mucosa bearing de novo carcinoma. METHODS: The expression of BGP and p53 protein in colorectal carcinoma using affinity purified specific anti-human BGP antibody (Ab) and anti-p53 Ab was studied using 96 resected specimens. Further investigation to examine the timing of BGP expression in comparison with p53 overexpression was carried out using 13, 18, eight, and 16 specimens of adenoma with mild, moderate, and severe dysplasia, and carcinoma in adenoma, respectively. The BGP immunohistochemistry in whole resected human colorectal mucosa (two with carcinoma and one with ulcer) was carried out using specific anti-BGP and anti-p53 Ab. RESULTS: The BGP visualized by immunohistochemistry was commonly present in colorectal carcinoma (83.3%). The expression of this molecule during ACS showed excellent correlation with the increased dysplasia and was found before p53 overexpression, whereas no BGP expression was seen in the normal human large intestine remote from the cancer foci. Positive staining in overtly normal-looking colonic mucosa was observed mainly around carcinomas without any adenoma component. CONCLUSIONS: The present study is the first to localize the BGP molecule in colorectal carcinoma, adenoma, and normal mucosa. It is suggested that BGP is a novel biomarker for carcinogenesis in both the pathways of ACS and the de novo colorectal carcinoma. [ABSTRACT FROM AUTHOR]

The expression of pancreatic secretory trypsin inhibitor (PSTI) was examined immunohistochemically in pulmonary adenocarcinoma. Of 86 carcinomas examined, 65 (76%) showed immunoreactivity for PSTI. Cases with the papillary subtype and those with early stage disease contained PSTI in cancer cells more frequently and were more strongly positive. There was a slight tendency to strong expression of PSTI in cases with the histologically well-differentiated type, tumor size of approximately 30 mm maximum diameter, and marked scar formation. Furthermore, 37 cases, which were the majority of the PSTI-positives, appeared to contain PSTI predominantly in cancer cells within the central or subpleural scar tissue and/or its surrounding tissue. Thus, pulmonary adenocarcinoma may commonly express PSTI and, considering previous reports that PSTI acts as a growth factor-like substance on fibroblasts in vitro in addition to the present findings of its immunohistochemical distribution in the tumor tissues, it is suggested that PSTI expressed in cancer cells of some pulmonary adenocarcinomas may possibly participate in tumor scar formation. Copyright © 1992 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The immunohistochemical localization of membrane-associated phospholipase A2 (M-PLA2) in normal human pancreases and 30 cases of pancreatic ductal carcinomas was investigated. In pancreatic ductal carcinomas, the immunoreactivity was observed in 25 cases (83%). Among the clinocopathological factors of pancreatic cancer, the incidence of expression of this enzyme is significantly higher in infiltrative type cancers. Furthermore, the expression of M-PLA2 was significantly increased in tumors, which had a larger amount of interstitial tissue. On the other hand, human M-PLA2 added exogenously to the fibroblast cell lines Swiss 3T3 and BALB/3T3 was found to augment their DNA synthesis. The stimulation of DNA synthesis was not affected by treatment with indomethacin. These results suggest that this enzyme could be involved directly in the proliferation of interstitial tissue through its own function. [Copyright &y& Elsevier]

Recently, differences in histological diagnosis of colonic neoplasms between Japan and Western countries have been noted. We examined the relationship between the histopathology and immunohistochemical localization of six genetically distinct type IV collagen α chains, the major component of basement membrane (BM), in normal and neoplastic colonic tissues. α1/α2(IV) and α5/α6(IV) chains were observed in normal mucosa and tubular adenomas with mild/moderate atypia. In non-invasive cancers, both α1/α2(IV) chains were linearly stained in the BM of cancer cell nests, while the assembly of α5/α6(IV) chains into the BM was inhibited in a discontinuous or negatively stained pattern. The differential expressions of the type IV collagen α5/α6 chains could be one of the diagnostic markers of the invasiveness of colon cancer. [Copyright &y& Elsevier]

To investigate the biological significance of skin-derived anti-leukoproteinase (SKALP)/elafin in squamous cell carcinoma (SqCC), the immunohistochemical expressions of SKALP/elafin in SqCC (lung 46 and esophagus 34) were studied. The results were compared with the immunohistochemical staining of a proliferating cell nuclear antigen (PCNA) and a TDT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay in serial sections. The expression of SKALP/elafin had a high incidence in SqCC (lung 82.6% and esophagus 73.5%). In contrast, no expression was observed in uninvolved bronchial epithelium and normal esophagus except for hyperplastic cells. SKALP/elafin expression was located in the cell layer just underneath the cornified envelope of each cell nest, and DNA fragmentation was observed in the same cell layer in which SKALP/elafin was expressed. PCNA expression was observed in the basal layer of each cornified envelope, and both expressions were clearly separated. In lung SqCC, immunoreactive score (IRS) of SKALP/elafin expression correlated significantly with the differentiation and it tended to increase in accordance with the degree of differentiation. In esophageal SqCC, there was also an obvious relationship between the expression of SKALP/elafin and its differentiation. There was no correlation between the expression and other clinicopathological factors. These results suggest that SKALP/elafin is possibly involved in the cell differentiation program, finally leading to keratinization in SqCC of human lung and esophagus. SKALP/elafin may be a beneficial molecular target for detection or even the development of a new therapeutic method against cancer. [Copyright &y& Elsevier]

The presence of RON and its variant isoform in malignant and non-malignant human colonic tissues was investigated by immunohistochemistry using paraffin-embedded sections and RT-PCR analysis followed by direct sequencing of PCR product using RNAs isolated from frozen tissues. In normal colonic mucosa of both human fetus and adult, RON was uniformly expressed in cript cells, especially in the bottom of cripta. On the other hand, the expression was distributed heterogeneously in adenomas and in colon cancer. The expression of RON was significantly related to the degree of differentiation of colon cancer. The RT-PCR analysis of RNA isolated from malignant and non-malignant colonic tissue revealed the presence of two RON mRNA isoforms. Direct sequencing of two major products was revealed to be identical to that of human wild-type RON and a splicing variant of RON transcript which has been reported in human gastric cancer cell line, KATO-III. It is indicated that both wild type RON and its valiant isoform play an important role in regulating the normal function of colonic mucosa such as differentiation and motile activity, and the expression of both wild-type RON and its valiant isoform could be considered to be reduced during malignancy of human colonic mucosa. [Copyright &y& Elsevier]