A Study of Biomarkers in Cervical Carcinoma and Clinical Correlation of the Novel Biomarker MN

Brewer, Cheryl A.; Liao, Shu-Yuan; Wilczynski, Sharon P.; Pastoreková, Silvia; Pastorek, J; Závada, Jan; Kurosaki, Tom; Manetta, Alberto; Berman, Michael L.; DiSaia, Philip J.; Stanbridge, Eric J.

doi:10.1006/gyno.1996.0333

Cited by 35 publications

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“…45 of 47 primary RCC (95%) were MN/CA IX/G250-positive, all clear cell tumours with or without granular/spindle cell expressing MN/CA IX/G250. Our extensive study with mAbG250 revealed an inverse correlation between MN/CA IX/G250 expression and tumour stage and grade, as described in other diseases (Brewer et al, 1996;Turner et al, 1997;Saarnio et al, 1998). Brewer et al (1996) have shown that low expression of MN/CA IX/G250 correlates with poor prognostic factors, e.g.…”

Section: Discussionsupporting

confidence: 79%

“…Although the functional significance of MN/CA IX/G250 in oncogenesis remains unclear, MN/CA IX/G250 can induce malignant phenotype in murine NIH 3T3 fibroblasts, suggesting that MN/CA IX/G250 plays a role in control of cell proliferation and transformation . In addition, recent reports confirmed that MN/CA IX/G250 may be useful as a potentially important biomarker for cervical carcinomas Brewer et al, 1996) and RCC (Liao et al, 1997;McKiernan et al, 1997). However, MN/CA IX/G250 MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas has also been detected in normal tissues in the alimentary tract .…”

mentioning

confidence: 89%

“…This antigen (MN/CA IX/G250) is a plasma membrane glycoprotein with an apparent molecular weight of 54/58 kDa, detectable in several types of malignancies; e.g. cervical and ovarian cancer (Liao et al, 1996), renal cancer (Oosterwijk et al, 1986), colorectal cancer (Saarnio et al, 1998), oesophageal cancer (Turner et al, 1997), bladder cancer (Uemura et al, 1996), but not in the normal tissues except alimentary tract, suggesting a possible role in oncogenesis. Sequential analysis has demonstrated that this gene (MN/ CA9/G250) is a novel member of the carbonic anhydrase (CA) family and MN/CA IX/G250 is considered to be the only tumourassociated CA isoenzyme.…”

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confidence: 99%

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MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas

et al. 1999

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SummaryThe monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently, G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PCR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs.

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Section: Discussionsupporting

confidence: 79%

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confidence: 89%

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confidence: 99%

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MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas

et al. 1999

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“…Reverse transcription was performed on 4 lg of total RNA. RNA was incubated for 10 min with oligo(dT) [12][13][14][15][16][17][18] at 65°C. After 10 min at room temperature, reaction reagents were added (SuperScript, Invitrogen, Carlsbad, CA) and incubated at 37°C for 1 hr.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Detection of carbonic anhydrase 9–expressing tumor cells in the lymph nodes of vulvar carcinoma patients by RT‐PCR

Kowalewska

Radziszewski

Kulik

et al. 2005

Intl Journal of Cancer

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Regional lymph node status is an important prognostic factor for vulvar cancer. The goal of our study was to elaborate a reliable test for detecting micrometastases, undetectable by traditional methods, in the lymph nodes of vulvar squamous carcinoma patients. For this purpose, carbonic anhydrase-9 (CA9) was investigated as a cancer-related marker by RT-PCR. Firstly, primary carcinoma specimens were examined for CA9 expression by immunohistochemistry with M75 monoclonal antibody. All 19 tissues exhibited a variable degree of staining, which was mostly confined to the plasma membranes of tumor cells. Correspondingly, all primary tumor specimens and the control A-431 vulvar cancer cell line gave a positive signal in the nested RT-PCR assay designed to detect CA9-expressing cells with a high sensitivity. Analysis of 77 lymph node specimens from 20 patients revealed a full correlation between RT-PCR results and standard hematoxylin-eosin staining in 75% of samples, whereas 25% of specimens were negative by the standard method and positive for CA9 mRNA, accounting for 28% of all histologically negative lymph nodes. There were no false-negatives with RT-PCR. A positive inguinal lymph node with a negative sentinel node was observed in the same groin only once in 38 specimens. Our findings clearly indicate potential value of CA9 as a molecular marker for the assessment of regional lymph node status in vulvar cancer patients and support a possible utility of our RT-PCR assay in the detection of micrometastases. ' 2005 Wiley-Liss, Inc.

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“…19,23 In addition, in patients with dysplastic lesions, it also stained morphologically normal endocervical cells instead of the clearly dysplastic cells, suggesting that the specificity and sensitivity of this marker is of limited clinical use for the diagnostic evaluation of cervical specimens. [23][24][25] Thus, there is still a significant demand for better biomarkers to identify dysplastic or neoplastic cervical epithelial cells precisely in biopsy samples and cervical smears.…”

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Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

et al. 2001

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Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through highrisk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16 INK4a . Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16 INK4a . In line with this hypothesis, we observed marked overexpression of p16 INK4a in all cervical intraepithelial neoplasm (CIN) I lesions (n ‫؍‬ 47) except those associated with low-risk HPV types (n ‫؍‬ 7), all CIN II lesions (n ‫؍‬ 32), all CIN III lesions (n ‫؍‬ 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16 INK4a was observed in normal cervical epithelium (n ‫؍‬ 42), inflammatory lesions (n ‫؍‬ 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n ‫؍‬ 7). Dysplastic cells could also be identified in cervical smears using a specific p16 INK4a monoclonal antibody. These data demonstrate that p16 INK4a is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears.

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A Study of Biomarkers in Cervical Carcinoma and Clinical Correlation of the Novel Biomarker MN

Cited by 35 publications

References 0 publications

MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas

MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas

Detection of carbonic anhydrase 9–expressing tumor cells in the lymph nodes of vulvar carcinoma patients by RT‐PCR

Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

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