Clinical implications of the epidermal growth factor receptor in the squamous cell carcinoma of the uterine cervix

Cancer of the cervix is the second most common malignancy among women worldwide. The last 20 years have lead to numerous advances in the medical management of locally advanced cervical cancer, including preventive vaccination, chemoradiation, and neoadjuvant chemotherapy. The treatment of metastatic disease is palliative at best. Platinum‐based chemotherapy remains the standard of care for inoperable patients who have recurrent disease. However, because most patients initially receive concomitant platinum‐based therapy with radiation, many recurrent tumors are refractory to platinum. The use of novel therapeutic approaches targeted to the carcinogenic processes that leads to the ontogenesis of cervical cancer should be promoted in clinical studies to improve patient outcomes. Cancer 2009; 115:3166–80. © 2009 American Cancer Society.

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“…EGFR is overexpressed in a wide variety of solid tumors, including cervical cancer. [51][52][53][54][55][56][57][58][59][60] In…”

Section: Biologic Agentsmentioning

confidence: 99%

Novel chemotherapy approaches for cervical cancer

Movva

Rodriguez

Arias-Pulido

et al. 2009

Cancer

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“…In the case of uterine cervical cancer, the incidence of EGFR overexpression has been variably reported to occur in 6 -85% of cases according to the detection techniques and methods used previously (7). Although there have been a few contradictory results (14), the majority of reports show that elevated levels of EGFR correlate with a more aggressive biological behavior and are clinically relevant to poor prognosis in cervical cancer patients (7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, activation of the EGFR signaling pathway enhances the transcription of the rate-limiting COX-2 gene in several cell types (15,(27)(28)(29)(30). Although both EGFR and COX-2 enzyme are known to play a vital role in oncogenic transformation, carcinogenesis, and tumor invasiveness (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(15)(16)(17), little information is available regarding the relationship between EGFR and COX-2 in cultured cervical carcinoma cell lines or in human cervical cancer. Moreover, the prognostic significance of the coexpressions of EGFR and COX-2 has not been investigated despite the fact that the separate overexpression of EGFR (7)(8)(9)(10)(11)(12)(13) or COX-2 (23-25) is known as an independent prognostic indicator in uterine cervical cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix

Kim

Cho³

et al. 2004

Clinical Cancer Research

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Results: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R 2 ‫؍‬ 0.05, P ‫؍‬ 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P ‫؍‬ 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P ‫؍‬ 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk ‫؍‬ 4.0, P ‫؍‬ 0.03).Conclusions: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.

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“…Increased expression of EFGR in the primary vulvar tumor was also significantly associated with lymph node metastases, but its predictive value was not properly addressed [14]. Studies on EGFR expression in other gynecologic malignancies showed that EGFR overexpression is associated with biological aggressiveness and poor prognosis in cervical cancer [20][21][22]. Multivariate analysis of risk factors for metastatic disease showed that EGFR overexpression in endometrial cancer is an independent predictor for the presence of metastases [23].…”

Section: Discussionmentioning

confidence: 99%

EGFR expression is associated with groin node metastases in vulvar cancer, but does not improve their prediction

Oonk

Bock²,

Veen

et al. 2007

Gynecologic Oncology

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Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractObjectives. High morbidity of elective inguinofemoral lymphadenectomy in early stage vulvar cancer patients urges the need for defining a group of low-risk patients in whom inguinofemoral lymphadenectomy can be safely omitted. Aim of the study was to evaluate whether in addition to 'classic' clinicopathological factors determination of EGFR expression in vulvar cancer can be helpful in defining such a 'low-risk' group.Methods. Formalin-fixed paraffin-embedded tumor tissue samples of 197 surgically treated T1/2 patients were collected in a Tissue Micro Array (TMA). On this TMA, immunohistochemistry for EGFR was performed. Logistic regression analyses were performed including histopathological characteristics with the presence of nodal metastases as outcome. A predictive model was constructed, and absolute risks were calculated.Results. EGFR expression was present in 68% of the vulvar tumors and related to the presence of lymph node metastases (OR 2.12, 95% CI 1.09-4.10). Our predictive model with only clinicopathological factors was able to define a group of patients with a likelihood of absence of lymph node metastases of 13% (95% CI 5-36), which could be decreased to 6% (95% CI 0-29) after inclusion of EGFR expression (p = 0.07).Conclusions. EGFR expression is present in the majority of vulvar tumors and is associated with groin node metastases in vulvar cancer. Current classic clinicopathological predictive factors for inguinofemoral lymph node metastases with or without EGFR analysis are not strong enough for identification of "sufficiently low" risk T1/2 vulvar cancer patients. Our predictive model approach however is excellent for evaluation of new cell biological parameters, associated with clinical outcome.

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Clinical implications of the epidermal growth factor receptor in the squamous cell carcinoma of the uterine cervix

Cited by 102 publications

References 12 publications

Novel chemotherapy approaches for cervical cancer

Novel chemotherapy approaches for cervical cancer

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix

EGFR expression is associated with groin node metastases in vulvar cancer, but does not improve their prediction

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