Dataset Information

Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.

ABSTRACT: Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutations in a cohort of 30 adenosquamous carcinomas of the uterine cervix.EGFR, PDGFRA and VEGFR2 immunohistochemistry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neoplastic area. Screening for EGFR (exons 18-21) and PDGFRA (exons 12, 14 and 18) mutations was done by PCR--single-strand conformational polymorphism (PCR-SSCP).Despite the presence of EGFR immunohistochemical positive reactions in 43% (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons 18-21) were identified. A silent base substitution (CAG>CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56%). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA>CCG) at codon 567 (P567P) in 9 cases and in exon 18 (GTC>GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14+3G>A and IVS14+49G>A) in two different cases, and in intron 18 (IVS18-50insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%), and was significantly associated with lack of metastasis (p=0.038).This is the most extensive analysis of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinomas. Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of adenosquamous carcinoma to specific anti-RTKs drugs.

SUBMITTER: Longatto-Filho A

PROVIDER: S-EPMC2711112 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.

Longatto-Filho Adhemar A Pinheiro Céline C Martinho Olga O Moreira Marise A R MA Ribeiro Luiz F J LF Queiroz Geraldo S GS Schmitt Fernando C FC Schmitt Fernando C FC Baltazar Fátima F Reis Rui M RM

BMC cancer 20090629

<h4>Background</h4>Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutation ...[more]

PMID: 19563658

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Project description:ObjectivesTo examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC.DesignNationwide, population based, nested case-control study.SettingSweden.ParticipantsAll cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling.Main outcome measuresConditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks.ResultsWomen with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test.ConclusionsCervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.

Project description:BackgroundDue to the rarity of adenosquamous carcinoma of the cervix (ASCC), studies on the incidence, prognostic factors, and treatment outcomes of ASCC remain scarce. Therefore, we performed a retrospective population-based study to systematically investigate the characteristics of ASCC patients.MethodsPatients with a histopathologically confirmed diagnosis of ASCC were enrolled from the Surveillance, Epidemiology, and End Results database between 1975 and 2016. Univariate and multivariate Cox regression analyses were performed to identify the potential predictors of cancer-specific survival (CSS) in patients with ASCC. Selected variables were integrated to establish a predictive nomogram and the predictive performance of the nomogram was estimated using Harrell's concordance index (C-index), calibration curve, and decision curve analysis (DCA).ResultsA total of 1142 ASCC patients were identified and included in this study and were further randomized into the training and validation cohorts in a 7:3 ratio. The age-adjusted incidence of ASCC declined from 0.19 to 0.09 cases per 100,000 person-years between 2000 and 2017, with an annual percentage change of -4.05% (P<0.05). We identified age, tumor grade, FIGO stage, tumor size, and surgical procedure as independent predictors for CSS in ASCC patients and constructed a nomogram to predict the 3- and 5-year CSS using these prognostic factors. The calibration curve indicated an outstanding consistency between the nomogram prediction and actual observation in both the training and testing cohorts. The C-index was 0.7916 (95% CI: 0.7990-0.8042) and 0.8148 (95% CI: 0.7954-0.8342) for the training and testing cohorts, respectively, indicating an excellent discrimination ability of the nomogram. The DCA showed that the nomogram exhibited more clinical benefits than the FIGO staging system.ConclusionsWe established and validated an accurate predictive nomogram for ASCC patients based on several clinical characteristics. This model might serve as a useful tool for clinicians to estimate the prognosis of ASCC patients.

Dataset Information

Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.

Publications

Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.

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