High SPINK1 Immunostaining in Colorectal Carcinoma is Associated with Poor Outcomes.

Objectives: Colorectal cancer (CRC) is the third most common cancer worldwide and is the second leading cause of cancer-related deaths. Serine protease inhibitor Kazal-type 1 (SPINK1) is found to be related to poor prognostic criteria and shortened overall survival of some malignancies such as liver, breast, lung, pancreatic and renal cancers. SPINK1 can be a potential biomarker for early detection and prediction of immune checkpoint blockade treatment response. Therefore, this study aimed to examine the possible role of SPINK1 in colorectal carcinogenesis and its prognostic ability.

Methods: This study used paraffin blocks of patients diagnosed with colorectal adenoma, primary CRC and available positive lymph node metastases. Specimens were obtained between April 2018 and June 2022 at the Department of Pathology, Faculty of Medicine, Minia University, Egypt. Immunohistochemistry was done for SPINK1 antibody and appropriate statistical analysis of results was performed.

Results: A total of 70 archival samples of CRC, 18 of colorectal adenoma and 20 of metastatic lymph nodes were used in this study. In a normal colon, there was a negative to weak SPINK1 immunostaining. High cytoplasmic immunostaining was seen in 57.1% of patients while low immunostaining in 42.9% of CRC. SPINK1 immunostaining was statistically associated with tumour grade (P = 0.024), stage (P <0.001), nodal status (P = 0.010), lymph node ratio (P = 0.044), lymphovascular invasion (P <0.001), tumour necrosis (P <0.001) and tumour infiltrating lymphocytes (P <0.001). No statistically significant association was found between SPINK1 and patient gender, age, tumour site, tumour size, histological subtype, perineural invasion, margin status and adenoma. A statistically significant association was detected between SPINK1 immunostaining in CRC and adenomas (P = 0.019) and between CRC and associated nodal metastasis (P = 0.013).

Conclusion: SPINK1 immunostaining is increased in CRC and associated with poor prognostic criteria and is significantly associated with immunoactivity in adenoma and associated nodal metastasis.