Abstract
Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen's data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p = 0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p = 0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p = 0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p = 0.016, r = 0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.
Highlights
Rectal cancer is one of the most malignant tumors in terms of incidence and prevalence [1, 2]
Preoperative chemoradiotherapy (CRT) combined with a total mesorectal excision (TME) is the standard treatment option for locally advanced rectal cancer (LARC) reducing rates of local recurrence [3, 4], while this approach seems to be more aggressive with patient burden, clinical toxicity resulting, as well as the financial cost care [5,6,7]
This study examined the expression of a panel of protein of mismatch repair protein (MMR), p53, HER-2, and Ki67 by immunohistochemistry as well as the mutational status of KRAS, NRAS, and BRAF genes by sequencing analysis and pyrosequencing
Summary
Rectal cancer is one of the most malignant tumors in terms of incidence and prevalence [1, 2]. The challenge of current medical research and numerous studies is to understand the different mechanisms of molecular pathways in malignant cells [8], as well as to comprehend the mechanisms of radiosensitivity and chemosensitivity in order to identify molecular biomarkers essential to guide therapeutic decisions and to individualize treatments of patients with rectal cancer [7, 9,10,11,12,13] To our knowledge, this is the first study on the possible predictive and prognostic roles of numerous markers in rectal pretreatment samples in Moroccan population. The potential predictive roles of biomarker expression and prognostic were evaluated
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