Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

Abstract

Objectives: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. Methods: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. Results: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07–26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. Conclusion: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.

Absence of Cyclooxygenase-2 Protein Expression is a Predictor of Tumor Regression in Rectal Cancer Treated with Preoperative Short-Term Chemoradiotherapy

“…High proliferative activity determined by proliferating cell nuclear antigen immunostaining and Ki-67 labeling were predictive of the response to preoperative CRT in patients with rectal canecr. 32,33 This study also suggested that neoadjuvant CRT induced COX-2 expression to COX-2-negative rectal cancer. The COX-2-positive rate in patients with rectal cancer was significantly increased after CRT.…”

“…2). 32,33 When there was a discrepancy in scoring between two investigators, consensus was achieved after discussion.…”

“…Several studies have reported immunohistochemical staining of p53 in patients with rectal cancer treated with radiotherapy. [30][31][32][33][34][35] However, the usefulness of p53 immunostaining as a predictive marker for CRT is still controversial.…”

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer

“…The inclusion of p21 screening is warranted, as the referenced studies in (Salonga, Danenberg et al 2000), (Lenz, Danenberg et al 1998). Numerous studies assessing TS expression have found that pretreatment biopsies negative for TS were predictive of response (Saw, Morgan et al 2003), (Diez, Ramos et al 2003), (Jakob, Liersch et al 2008), (Negri, Campanini et al 2008). 3 studies revealed a better outcome with low or absent pretreatment TYMS expression, however another study demonstrated better outcome with high TYMS expression.…”

Role of thymidylate synthase as a predictor of neoadjuvant chemoradiation therapy in rectal cancer

“…Ряд исследований выявил зависи-мость между хорошим ответом опухоли на неоадъювантную терапию и низкой экспрессией тимидилатсинтетазы (или во-обще её отсутствием), однако другие ра-боты свидетельствуют об обратной связи: между значительной регрессией опухоли и высокой экспрессией тимидилатсинтетазы [5][6][7][8]. Однако работы, определившие корре-ляцию между регрессией опухоли в ответ на неоадъювантную радиохимиотерапию и высокой экспрессией тимидилатсинтетазы, на проводимую химиолучевую терапию (с преобладанием больных с низкой экспрессией) и полной регрессией опухоли (с преобладанием больных с высокой экспрессией).…”