Squamous cell carcinoma of the head and neck commonly affects patients in their sixth decade and older, particularly those with a prolonged history of alcohol and tobacco abuse. Less frequently, carcinomas occur in young individuals even in the absence of known risk factors. The purpose of this study is to investigate a possible relationship between these tumors and human papilloma virus (HPV). Thirty-three cases of squamous cell carcinoma of the head and neck in young patients under the age of 40 years were studied: 15 oral, 11 tonsillar, and 7 laryngeal. HPV DNA was detected by polymerase chain reaction in 10 tonsillar and 2 laryngeal carcinomas and in none of the oral tumors. Of the 12 HPV-positive tumors, 11 were HPV16 and 1 was HPV31. HPV-positive tumors had a distinct nonkeratinizing basal cell morphology, they stained diffusely and strongly with p16 antibodies, had higher Ki-67 and lower p53 staining scores as compared with the conventional keratinizing HPV negative carcinomas. It is concluded that in young patients high-risk HPV, particularly HPV16, is strongly associated with tonsillar squamous cell carcinoma and some cases of laryngeal, but not oral, tumors. The HPV-positive carcinomas have a distinct histopathologic and immunophenotypic features.

Individual classes of human endogenous retrovirus (HERV) genes and proteins are expressed in cancer, but expression of more than one type of HERV is rare. We report here the expression of multiple HERV genes and proteins in ovarian cell lines and tissues. Expression of HERV-K env mRNA was greater in ovarian epithelial tumors than in normal ovarian tissues (N 5 254). The expression of this protein on the surface and in the cytoplasm of ovarian cancer cells was confirmed using anti-HERV-K specific antibody by flow cytometric analysis. The frequency of expression of HERV-K env protein in multitissue microarrays (N 5 641) was determined by immunohistochemistry and a significant correlation with tumor histotype was found. A significantly increased expression of HERV-K was observed in tumors with low malignant potential and low grade, relative to expression in normal ovarian tissues. The increase in expression of HERV-K env protein took place in a stepwise fashion in serous papillary adenocarcinoma. Interestingly, we found that other classes of HERV env mRNAs, including ERV3 and HERV-E, are expressed in the same ovarian cancer tissues that expressed HERV-K. Furthermore, anti-HERV antibodies including anti-ERV3 (30%), anti-HERV-E (40%) and anti-HERV-K (55%) were detected in patients with ovarian cancer, but not in normal female controls. HERV env proteins are frequently transcribed and translated in ovarian epithelial tumors, and multiple HERV families are detectable in ovarian cancer. HERV env proteins, and especially those expressed on the cell surface, may serve as novel tumor targets for detection, diagnosis and immunotherapy of ovarian cancer. ' 2006 Wiley-Liss, Inc.

BACKGROUNDThe expression of human endogenous retrovirus (HERV) mRNA and proteins was associated recently with diseases that include human malignancies. The authors report that, in the current study, transcripts encoding the envelope region of an HERV family, HERV‐E, were expressed in human prostate carcinoma.METHODSRNA was isolated from various prostate tissues and was tested for the expression of various HERV envelope (env) genes by reverse transcriptase–polymerase chain reaction (RT‐PCR) analysis, RNA in situ hybridization (ISH), and Northern blot analysis. Variants of HERV that appeared in prostate carcinoma tissues were sequenced, and HERV‐E was expressed in prokaryotic and eukaryotic systems.RESULTSIn the current study, the authors found that the mRNA of the env gene of one particular family of HERVs, HERV‐E, was expressed in some prostate carcinoma tissues (38.8% positive; n = 49 specimens) but not in normal prostate tissues using RT‐PCR, RNA ISH, and Northern blot assays. The expression of HERV‐E transcripts in prostate tumor epithelial cells was confirmed further by ISH using an HERV‐E specific antisense probe. Approximately 50% of the cDNA of HERV‐E obtained from prostate carcinoma specimens contained no stop codon and expressed proteins in prokaryotic or eukaryotic expression systems. Furthermore, the expression of both HERV‐E and ERV3 (another class of HERV) was detected in the same prostate carcinoma tissues.CONCLUSIONSThe expression and distribution of multiple HERV‐E endogenous retroviral elements in prostate carcinoma, but not in normal control specimens, suggests that they may serve as novel tumor markers for the early diagnosis and immunotherapy of patients with prostate carcinoma. Cancer 2003;98:187–97. © 2003 American Cancer Society.DOI 10.1002/cncr.11451

Human endogenous retroviruses (HERVs) comprise up to 8% of the human genome. In previous studies, we demonstrated that type 1 HERV-K envelope (env) transcripts are expressed in most human breast cancers, but not in normal breast tissues. In the current study, we report that type 2 HERV-K env transcripts are also present in human breast cancers. By real-time RT-PCR, the expression of HERV-K env transcripts was 5-10-fold higher in breast cancer cell lines treated with estradiol and progesterone than in cells without treatment, and expression was significantly higher in most breast cancer tissues than in normal breast tissues. Furthermore, both types of HERV-K env transcripts were capable of being spliced into subgenomic env transcripts and various splice donor and acceptor sites were detected in breast cancers. The selective expression and distribution of multiple HERV-K endogenous retroviral element splice variants in breast cancer, but not in normal controls, suggests that they are novel breast tumor markers.

Primary adenocarcinoma of the urinary bladder sometimes causes a diagnostic dilemma because it can be indistinguishable morphologically from adenocarcinoma of colorectal origin secondarily involving the bladder by metastasis or direct extension. It is much less well studied than conventional urothelial carcinoma and colorectal adenocarcinoma because of its rarity. The current study was specifically designed to investigate whether an important mechanism involved in the pathogenesis of colorectal adenocarcinoma, beta-catenin dysregulation, was also important for the development of primary bladder adenocarcinoma and whether these two morphologically similar tumors could be distinguished immunohistochemically. Formalin-fixed, paraffin-embedded tissues from 17 primary adenocarcinomas of the urinary bladder, 16 colorectal adenocarcinomas involving the bladder, and 10 conventional urothelial (transitional) carcinomas were included in this study. Thirteen of the primary bladder adenocarcinomas were moderately to well differentiated (enteric type) and morphologically indistinguishable from colorectal cancers. The remaining four primary tumors were poorly differentiated (two cases) or of clear cell type (two cases). Immunohistochemical studies using a panel of monoclonal antibodies demonstrated positive nuclear staining for beta-catenin expression in 13 of the 16 (81%) colorectal adenocarcinomas secondarily involving the bladder but in none of the primary adenocarcinomas or the urothelial carcinomas. Instead, positive membranous (and some cytoplasmic) staining was present in all primary bladder tumors with the exception of two poorly differentiated adenocarcinomas where no beta-catenin staining was detected. All secondary colorectal adenocarcinomas stained negatively for CK7 and thrombomodulin (TM), whereas positivity for CK20 was observed in 15 (94%) cases. All urothelial carcinomas stained positively for CK7 and TM, and four of them also for CK20. Primary adenocarcinomas of the bladder showed mixed staining patterns for CK7, CK20, and TM with a positive rate of 65%, 53%, and 59%, respectively. These data indicate that dysregulation of beta-catenin, an important aberration seen in colorectal carcinogenesis, does not appear to play a role in the pathogenesis of the bladder adenocarcinoma. In addition, our data demonstrate that a panel of immunostains, including CK7, CK20, TM, and beta-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.