Although the overexpression of cyclin D1 has been believed to play important roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen's disease (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell carcinoma (BCC), were investigated immunohistochemically using monoclonal antibody to cyclin D1 by the LSAB method, to assess the expression of cyclin D1 in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respectively. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, only 2 cases, 1 of SCC and 1 of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dysplasia of BCC was correlated with age. Expression of cyclin D1 markedly increased from normal skin through dysplasia to BOD, but was not significantly related to the degree of SCC differentiation. These findings demonstrate that the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is not increased. Comparison with the results for p53 protein expression in these tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 years old. These findings suggested the hypothesis that prior aberrant p53 expression may affect or regulate the overexpression of cyclin D1.

Multinucleated giant cells (MGC) detected in the submucosal layer of human urinary bladder mainly associated with transitional cell carcinoma were examined immunohistochemically and ultrastructurally. The cases examined totaled 29, namely 14 cases with transitional cell carcinoma and another 15 cases mostly with malignancy in other organs. Histologically, MGC were smooth, irregular or dendritic in shape, and tended to increase in number in the vicinity of cancer or marked inflammation. They were consistently positive for not only vimentin, but also MB-2, and CD34, and were mostly positive for proliferating cell nuclear antigen (PCNA), but not MIB-1 (Ki-67) and HLA-DRalpha antigens. On occasion, antibodies to alpha-smooth muscle actin (alpha-SMA), muscle actin (M-actin), CD68 (KP-1) and alpha subunit of S-100 protein also yielded positive reactions. Interestingly, aggregated short bulbous processes were ultrastructurally observed on their surface in parts. These findings suggested that MGC in the submucosal layer of human urinary bladder were MB-2 and CD34-positive multipotential mesenchymal cells with no mitotic activity expressing fibroblastic (vimentin), myofibroblastic (alpha-SMA), or histiocytic (CD68) markers mostly in the vicinity of malignancy, and that these MGC were formed by fusion of mononuclear cells expressing identical markers with those of MGC. Further investigations are needed to clarify the exact function of MGC in human urinary bladder.

We applied an in situ polymerase chain reaction (PCR) hybridization method in order to detect human T-lymphotropic virus type I-infected cells in routinely-processed paraffin sections of the lung from 13 autopsied patients with adult T-cell leukemia (ATL). Previously reported protocol resulted in somewhat non-specific staining in our sections. Therefore, we used a hot start PCR method using specialized commercially-available polymerase in order to increase the specificity. Of 6 patients with ATL cell invasion into the lungs, 4 exhibited strong positive staining of almost all invading ATL cells. In contrast, 7 patients without ATL cell invasion into the lungs did not demonstrate any significant reactivity. Since the method described here is a relatively simple hot start method and does not yield false-positives, it may allow us to determine whether human T-lymphotropic virus type I (HTLV-I) associated disorders are related to lymphocytes integrating the HTLV-I genome.

HistopathologyVolume 35, Issue 1 p. 87-88 H-cadherin expression in breast cancer T Takeuchi, T Takeuchi Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorA Misaki, A Misaki Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorB-K Chen, B-K Chen Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorY Ohtsuki, Y Ohtsuki Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this author T Takeuchi, T Takeuchi Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorA Misaki, A Misaki Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorB-K Chen, B-K Chen Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this authorY Ohtsuki, Y Ohtsuki Department of Pathology, Kochi Medical School, Nankoku, Kochi, JapanSearch for more papers by this author First published: 10 December 2003 https://doi.org/10.1046/j.1365-2559.1999.0728c.xCitations: 19Read the full textAbout ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume35, Issue1July 1999Pages 87-88 RelatedInformation

To examine the expression of c-Met protein in thyroid tumors and the correlation of c-MET protein expression with lymph node metastasis (LNM) and pathological stage, 111 papillary thyroid carcinomas (PTC), including 44 with synchronous LNM, and 117 follicular adenomas (FA) were immunohistochemically examined using dewaxed sections of formalin-fixed, paraffin-embedded tissues. Immunohistochemical results were confirmed by Western blot analysis. For PTC, positive immunostaining was observed in 107 of 111 (96.4%) cases and was diffusely present in either cytoplasm and nucleus, or only cytoplasm or only nucleus of cancer cells at varying intensities. Staining tended to be stronger in the periphery of cancer cell nests. Positive reaction was also found in 44 of 117 (37.6%) cases of FA. However, the extent and intensity of c-Met immunostaining in FA were far less than those in PTC (p < 0.0001). Forty-four PTC cases (39.6%) exhibited LNM, and the extent and intensity of c-Met expression were significantly correlated with both LNM (p < 0.0001) and pathological stage (p < 0.0001). No significant correlation of c-Met expression with age, sex or tumor size was found. Our findings suggest that PTC expresses c-Met protein much more strongly and intensively than does FA, and that strong and intense overexpression of c-Met protein may be an indicator of the presence of lymph node metastasis and advanced pathological stage of papillary thyroid carcinoma.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.

Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm, of which the histogenesis is still controversial. Here we report a case of OGTP involving the head of the pancreas in a 71-year-old woman with metastases to the gallbladder and lymph nodes. The primary and metastatic tumors had identical histopathological, immunohistochemical, ultrastructural and molecular biological features. Microscopically, the tumors were characterized by atypical, often pleomorphic mononuclear cells associated with the proliferation of benign-appearing osteoclast-like giant cells (OGCs). Electron microscopic observation provided ultrastructural evidence of epithelial differentiation of the mononuclear cells, including microvilli and desmosomes, which was not obtained for OGCs. On immunohistochemical study, OGCs stained for CD68 (KP-1), LCA and HAM56, whereas mononuclear cells only reacted with PCNA. These findings clearly suggest that mononuclear cells are capable of differentiation and proliferation and may have been the only true tumor cells in this neoplasm, and that OGCs may have been a paraneoplastic product of this rare tumor. On examination of DNA from dewaxed sections of the tumor, we found no p53 mutation in the tumor tissue, but found two K-ras mutations in colon' 12; this pattern of mutation commonly occurs in pancreatic carcinoma, indicating a somewhat genetic relationship of OGTP to pancreatic carcinoma. Although OGTP often has a favorable prognosis, the outcome in the present case was poor due to early tumor spread, with less than two years postoperative survival.

A novel human cDNA containig CAG repeats, designated B120, was cloned by PCR amplification. An approximately 300-bp 3′ untranslated region in this cDNA was followed by a 3426-bp coding region containing the CAG repeats. A computer search failed to find any significant homology between this cDNA and previously reported genes. The number of CAG trinucleotide repeats appeared to vary from seven to 12 in analyses of genomic DNA from healthy volunteers. An approximately 8-kb band was detected in brain, skeletal muscle and thymus by Northern blot analysis. The deduced amino-acid sequence had a polyglutamine chain encoded by CAG repeats as well as glutamine- and tyrosine-rich repeats, which has also been reported for several RNA binding proteins. We immunized mice with recombinant gene product and established a monoclonal antibody to it. On Western immunoblotting, this antibody detected an approximately 120-kDa protein in human brain tissue. In addition, immunohistochemical staining showed that the cytoplasm of neural cells was stained with this antibody. These findings indicated that B120 is a novel cDNA with a CAG repeat length polymorphism and that its gene product is a cytoplasmic protein with a molecular mass of 120kDa.