The p16 protein (p16) is a cyclin-dependent kinase (CDK) inhibitor that decelerates the cell cycle by in-Many studies have shown that human papillomavirus (HPV) infection plays an important role in cervical carcinogenesis.1 In fact, HPV infection has been detected in almost all preneoplastic and neoplastic lesions of the cervix. Recent extensive studies have revealed the existence of more than 70 subtypes of HPV, of which approximately 20 can infect the cervical epithelium and give rise to various lesions of the cervix.1-3 Moreover, each HPV subtype has been shown to be associated with a different risk of neoplastic transformation by cervical epithelial cells, and the HPV subtypes have been classified into three categories according to the risk: high, intermediate, and low.2,3 HPV-16 and -18 are representative of highrisk HPVs and are the most clinically important HPV subtypes, because infection by these viruses has a marked influence on outcome. HPV-31, -33, -35, -51, -52, and -58 are associated with intermediate risk for development of cervical cancer and high-grade squamous intraepithelial lesions (HSILs), whereas HPV-6 and -11 are classified as low-risk HPVs and are usually associated with benign hyperplastic lesions such as condylomata acuminata and low-grade squamous intraepithelial lesions (LSILs).

Both p16 and retinoblastoma (Rb) proteins are important tumor suppressors that regulate the cell cycle. The status of both proteins in invasive cervical cancer and cervical intraepithelial neoplasia (CIN) has not yet been examined. The aim of this study was to investigate the expression of p16 and Rb proteins by immunohistochemistry using 98 formalin-fixed and paraffin-embedded samples of various cervical neoplastic lesions. Strong immunoreactivity for the p16 protein was observed in both the nuclei and cytoplasm of all CIN and invasive cancer cases except several low-grade CIN lesions. Expression of Rb protein was also demonstrated in the scattered nuclei of neoplastic and normal cells in all cases investigated. The results suggest that the deletion or mutational inactivity of both p16 and Rb proteins may be a rare event in cervical carcinogenesis. Moreover, overexpression of the p16 protein may be a useful diagnostic marker for cervical neoplastic lesions on routine laboratory screening.

In order to clarify the frequency of p16 gene inactivation and its relationship with Rb expression, immunohistochemical analysis of p16 and Rb proteins was carried out on 82 paraffin‐embedded sections of primary non‐small cell lung cancers (NSCLCs). From immunohistochemical results, abnormal p16 expression was observed in 66% of NSCLCs, 80% in squamous cell carcinomas and 46% in adenocarcinomas. An inverse correlation between p16 and Rb expressions was noted. Moreover, the methylation status of the p16 gene was investigated by the methylation‐specific polymerase chain reaction (MS‐PCR) using 29 frozen samples of NSCLCs. MS‐PCR revealed the methylation of the p16 gene in 10 (34%) of 29 NSCLCs. All NSCLCs exhibiting methylation exhibited abnormal p16 expression and were positive for Rb. In NSCLCs, no difference in methylation status was observed with respect to clinico‐pathological characteristics including histological subtype and tumor stage. Our results demonstrate that abnormality of p16 expression is frequent in primary NSCLCs and methylation of the promoter of the p16 gene occurs in 34% of primary NSCLCs, which might play a significant role in the inactivation of the p16<0R> gene. Int. J. Cancer (Pred. Oncol.) 79:215–220, 1998.© 1998 Wiley‐Liss, Inc.

To understand the interaction between hepatocyte growth factor (HGF) and its receptor c-Met on various bone and soft tissue tumors, their expressions were investigated by western blot analysis, immunohistochemistry and enzyme immunoassay. Western blot analysis revealed that c-Met protein was expressed in 21 (38.8%) of 54 tumors, which detailed to seven (25.9%) of 27 bone tumors and 14 (51.8%) of 27 soft tissue tumors. Most malignant fibrous histiocytomas (MFH) and all neurofibromas expressed c-Met protein. The highest expression of c-Met protein was seen in a case of biphasic synovial sarcoma, where its immunoreactivity was localized only on the epithelial component and not on the sarcomatous component. By enzyme immunoassay for HGF, all but one MFH showed HGF production and the mean level of HGF was the highest among the tumors investigated. Neurofibromas and osteosarcomas had the next highest mean levels of HGF production, respectively. Coexpression of HGF and c-Met was observed in 19 (35.2%) of 54 tumors and was frequently observed in neurofibroma, followed by MFH and synovial sarcoma. Although the mode of interaction between HGF and c-Met varies among the various bone and soft tissue tumors including MFH, their signaling system may play an important role in the development and progression of bone and soft tissue tumors.

Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC.

Regional lymph nodes of Küttner's tumor from 3 patients showed reactive follicular hyperplasia and prominent interfollicular plasmacytosis. The patients were 71-, 57-, and 73-year-old Japanese men. The polytypic nature of plasma cells was demonstrated by immunohistochemistry. There were numerous IgG-positive plasma cells with scattered IgA-positive or IgM-positive plasma cells. IgG4-positive cells comprised 25% to 40% of IgG-positive plasma cells. Prominent polyclonal hyperimmunoglobulinemia was demonstrated on laboratory test in 2 cases examined. An elevated serum IgG4 level (16%) was also demonstrated in 1 patient. The present 3 cases indicated that regional lymph node of Küttner's tumor may show reactive follicular hyperplasia and prominent interfollicular plasmacytosis and should be differentiated from various benign and malignant lymphoproliferative disorders including systemic rheumatic disease, plasma cell type of Castleman disease, and lymph node involvement of marginal B-cell lymphoma of the mucosa-associated lymphoid tissue type showing prominent plasma cell differentiation.

No abstract

No abstract