Abstract
Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide and is the second most frequent cause of cancer-related mortality in Japan [1]
Short-term results were reported from a national trial (FOxTROT trial) in which oxaliplatin-based neoadjuvant chemotherapy was administered for CRC with predicted stages T3-4, N0-2, and M0
For stage II/III CRC, we previously demonstrated that MSLN expression is a robust independent prognostic factor using standard sections, which were the maximum sections that included the invasive margin of the cancer [13]
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide and is the second most frequent cause of cancer-related mortality in Japan [1]. For stage II/III CRC, the standard treatment in the country is to initially perform radical resection and subsequently provide adjuvant chemotherapy based on the pathological findings of the resected specimen [2]. Short-term results were reported from a national trial (FOxTROT trial) in which oxaliplatin-based neoadjuvant chemotherapy was administered for CRC with predicted stages T3-4, N0-2, and M0. Patients in the neoadjuvant chemotherapy group tended to have lower 2-year postoperative recurrence rates (neoadjuvant chemotherapy vs postoperative adjuvant chemotherapy, 13.6% vs 17.2%; P = 0.08) [4]. If patients with a high risk of recurrence could be identified prior to treatment, the benefit of preoperative treatment could be evaluated in this group
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