Abstract
Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.
Highlights
Cervical carcinoma is the fourth most common cancer in women, and the seventh overall, with estimated 528,000 new cases and 266,000 deaths from this viralinduced cancer worldwide in 2012 [1].In Sweden, 467 new cases were recorded in 2013, accounting for 1.8% of all female cancers, and 142 deaths
In the present study we have studied the expression of β-catenin, axin and adenomatous polyposis coli (APC) in a consecutive series of 122 cervical cancer (FIGO stages I-IV) patients treated with external beam radiotherapy and brachytherapy by immunohistochemistry (IHC) using tissue microarray (TMA)
Our series of cervical carcinomas were treated with combined radiotherapy, external pelvic beam therapy and brachytherapy, and as we know cell apoptosis is an important mechanism for the treatment effect and death of the tumor cells after radiotherapy
Summary
Cervical carcinoma is the fourth most common cancer in women, and the seventh overall, with estimated 528,000 new cases and 266,000 deaths from this viralinduced cancer worldwide in 2012 [1]. In Sweden, 467 new cases were recorded in 2013, accounting for 1.8% of all female cancers, and 142 deaths. In the developed world most patients present with early disease, either confined to the cervix or with limited extension beyond it (FIGO stages IB1-IIA). Radical hysterectomy with node dissection and radical radiotherapy are two options both giving 5-year survival rates of 80-90%. Intracavitary brachytherapy (ICBT) plays an important role in the management of patients with cervical cancer in most stages (I-IV). The combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) [6] and concomitant chemotherapy has become standard of care for locally advanced disease [7]
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