Carbonic anhydrase IX is strongly overexpressed in adenocarcinoma in situ of the cervix uteri.
ABSTRACT Adenocarcinoma in situ (AIS) or high grade cervical glandular intraepithelial neoplasia comprises approximately one percent of cervical in situ lesions and is well accepted as precursor of invasive adenocarcinoma.(1) High-risk human papilloma virus infection has been demonstrated as the most important causative agent of AIS. At present, however, we still know far less about metabolic features of these lesions This article is protected by copyright. All rights reserved.
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ABSTRACT: A new tumor-associated antigen, MN, has been identified whose expression correlates with the tumorigenic phenotype of HeLa x fibroblast somatic cell hybrids. Because HeLa is a cell line derived from a cervical carcinoma, we investigated the diagnostic utility of MN expression in cervical neoplasia. It was found that normal cervical tissue does not express the antigen, or does so in occasional focal areas of weakly staining reserve cells. In contrast, significant immunoreactivity (immunoperoxidase staining of paraffin-embedded sections) was observed in cervical intraepithelial neoplasias, adenocarcinoma in situ, and frank carcinomas, both squamous cell and adenocarcinoma. Varying patterns of immunoreactivity were observed and were characterized as diffuse, diffuse/focal, or focal. Greater than 90% of dysplastic or malignant tissues showed immunoreactivity. An interesting observation was that normal cervical tissue associated with cervical intraepithelial neoplasias, or adenocarcinoma in situ showed a staining pattern in the reserve cells and/or normal columnar cells that approximated the level of intensity exhibited by the dysplastic tissue. These results indicate that MN antigen expression has potential utility as a biomarker of cervical neoplasms.American Journal Of Pathology 10/1994; 145(3):598-609. · 4.60 Impact Factor
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ABSTRACT: An acidic extracellular pH is a fundamental property of the malignant phenotype. In von Hippel-Lindau (VHL)-defective tumors the cell surface transmembrane carbonic anhydrase (CA) CA9 and CA12 genes are overexpressed because of the absence of pVHL. We hypothesized that these enzymes might be involved in maintaining the extracellular acidic pH in tumors, thereby providing a conducive environment for tumor growth and spread. Using Northern blot analysis and immunostaining with specific antibodies we analyzed the expression of CA9 and CA12 genes and their products in a large sample of cancer cell lines, fresh and archival tumor specimens, and normal human tissues. Expression was also analyzed in cultured cells under hypoxic conditions. Expression of CA IX and CA XII in normal adult tissues was detected only in highly specialized cells and for most tissues their expression did not overlap. Analysis of RNA samples isolated from 87 cancer cell lines and 18 tumors revealed high-to-moderate levels of expression of CA9 and CA12 in multiple cancers. Immunohistochemistry revealed high-to-moderate expression of these enzymes in various normal tissues and multiple common epithelial tumor types. The immunostaining was seen predominantly on the cell surface membrane. The expression of both genes was markedly induced under hypoxic conditions in tumors and cultured tumor cells. We conclude that the cell surface trans-membrane carbonic anhydrases CA IX and CA XII are overexpressed in many tumors suggesting that this is a common feature of cancer cells that may be required for tumor progression. These enzymes may contribute to the tumor microenvironment by maintaining extracellular acidic pH and helping cancer cells grow and metastasize. Our studies show an important causal link between hypoxia, extracellular acidification, and induction or enhanced expression of these enzymes in human tumors.American Journal Of Pathology 04/2001; 158(3):905-19. · 4.60 Impact Factor
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ABSTRACT: A relative and an absolute increase in the incidence of adenocarcinoma of the uterine cervix has occurred in the United States since 1970. Currently, most pathologists recognize the histologic and cytologic features of invasive adenocarcinoma of the cervix, but there is confusion surrounding the histologic features and biologic behavior of adenocarcinoma in situ, endocervical glandular dysplasia, and the definition of microinvasive adenocarcinoma of the cervix. Similarly, the distinction of in situ adenocarcinoma from an early invasive adenocarcinoma of the cervix may be problematic. This article focuses on the histologic criteria, biologic behavior, and some approaches to therapy for these challenging lesions. General conclusions based largely on published studies include the following: 1) adenocarcinoma in situ (AIS) is a recognizable precursor to invasive adenocarcinoma and can be divided according to distinct histologic subtypes; 2) AIS is multifocal or involves multiple quadrants of the cervix in about half of cases; 3) AIS can be cured by simple hysterectomy and in many cases may be treated effectively by cone biopsy; 4) endocervical glandular dysplasia is not a reproducibly recognizable lesion, and its behavior and existence are undefined; 5) criteria exist to permit the distinction of early invasive adenocarcinoma from AIS in about 80% of cases; 6) microinvasive adenocarcinoma of the cervix is complicated by the presence of multiple definitions; clinical decision making is best guided by assessment and reporting of the depth, horizontal extent, and presence of lymphatic or vascular invasion.International Journal of Gynecological Pathology 11/2002; 21(4):314-26. · 1.63 Impact Factor