ERCC1, PARP-1, and AQP1 as predictive biomarkers in colon cancer patients receiving adjuvant chemotherapy

Article type: Research Article

Authors: Abdelrahman, Aziza E.^{a; *} | Ibrahim, Doaa Abdelaziz^a | El-Azony, Ahmed^b | Alnagar, Ahmed A.^c | Ibrahim, Amr^d

Affiliations: [a] Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt | [b] Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt | [c] Medical Oncology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt | [d] General Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence: [*] Corresponding author: Aziza E. Abdelrahman, Pathology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt. Tel.: +20 1068743218; E-mail: azaelsayed@gmail.com.

Abstract: BACKGROUND: The recognition of high-risk colon cancer patients prone to chemoresistant and recurrent disease is a challenge. OBJECTIVES: We aimed to assess the immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy. Their predictive role of tumor progression and disease-free survival (DFS) was analyzed. METHODS: The immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy was studied. The collected data on the overall survival (OS), disease-free survival (DFS), and the response to the chemotherapy were analyzed. RESULTS: Positive nuclear ERCC1 expression was identified in 58.3% of the patients, ERCC1 expression was significantly associated with left-sided tumors (P< 0.01). Moreover, its expression was significantly associated with the aggressive tumor characteristics including high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). High nuclear PARP-1 expression was observed in 63.3% of the cases, and its expression was significantly associated with tumor grade and lymph node metastasis (P= 0.003 for each). Positive membranous AQP1 expression was identified in 41.7% of patients, and it was associated with high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). During the follow-up period, 23 patients (38.3%) exhibited a tumor progression; this was significantly associated with positive ERCC1, high PARP-1, and negative AQP1 expression. Statistics of the survival data revealed that shorter DFS was significantly associated with positive ERCC1, high PARP-1, and positive AQP1 expression (P= 0.005, 0.016, 0.002, respectively). CONCLUSIONS: ERCC1, PARP1, and AQP1 are adverse prognostic biomarkers in stage II–III colon cancer. Moreover, adjuvant chemotherapy may not be beneficial for patients with positive ERCC1, high PARP1, and AQP1-negative tumors. Therefore, we recommend that ERCC1, PARP-1, and AQP1 should be assessed during the selection of the treatment strategy for stage II–III colon cancer patients.

Keywords: Colon cancer, ERCC1, PARP-1, AQP1, immunohistochemistry

DOI: 10.3233/CBM-190994

Journal: Cancer Biomarkers, vol. 27, no. 2, pp. 251-264, 2020