Investigating the relationship CLCA4 expression and prognostic and survival in breast canser patients

Breast cancer is the most common cancer in women in the world and in Turkey, according to 2020 data. It accounts for 15% of cancer-related deaths in women. In recent years, because of development of imaging and scanning systems and targeted molecular therapies, decrease in mortality is observed. There are many factors that affect the prognosis of breast cancer. The main ones of these factors are age, tumor size, histological grade, histological type of tumor, hormone receptor status, lymphovascular invasion, lymph node metastasis, and distant organ metastasis. Calcium-activated chloride channel (CLCA) is protein that have a symmetrical homocysteine motif in the terminal tail of the amino group. CLCA proteins play an important role in chloride effectiveness in epithelial cells. Epithelial-to-mesenchymal transition (EMT) is developmental program that down-regulates cell-cell connections, acquires spindle cell morphology and exhibits cellular mobility. EMT in breast cancer facilitates invasion of surrounding tissues and also is thought to be closely related to cancer metastasis and recurrence. CLCA4 is thought to inhibit cell migration and invasion by suppressing mesenchymal transition from epithelium via PI3K/ATK signaling pathway. Our study includes 150 cases that 90 cases diagnosed with invasive breast carcinoma-NOS (invasive ductal carcinoma), 30 case diagnosed with invasive lobular carcinoma, 30 cases diagnosed with mixed breast cancer in mastectomy materials sent to Fırat University Hospital Medical Pathology Department Laboratory between January 2010-June 2016. Control tissues is chosen from 10 cases among these 150 cases with sufficient breast tissue in non-tumor areas. Age of the patients, axillary lymph node metastasis, tumor diameter, bloom Richardson score and survival status were accessed from the digital archiving system. Immunohistochemical CLCA4 staining was applied to the sections made from selected paraffin blocks. CLCA4 immune score and other prognostic values were compared statistically. There was a significant difference between CLCA4 immune score of the groups (p<0.001). Significant differences in immune score were observed between normal breast tissues and tumor areas and it was found to be expressed higher in normal tissue. A negative significant correlation was found between CLCA-4 scores and tumor diameter. In dead patients, CLCA4 immune score (p=0.005) and follow-up time (p<0.001) were significantly lower than survived patients. Significant correlation is not found between CLCA4 score and other prognostic factors. In conclusion; we observed that decreased expression of CLCA4, activates EMT and increases tumor diffusion. This study proved that CLCA4 may be an effective predictor of prognosis and multivariate survival analysis because of negative correlations of tumor diameter and survival.