Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators.

We have investigated the distribution of chemokine receptor 4 (CXCR4) and CD8-positive, tumour-infiltrating T lymphocytes (CD8+ TILs) in breast cancer subtypes and explored the relationship between them and the well-established conventional prognostic markers, including axillary lymph node involvement. A total of 250 breast cancer patients were included in the study. The patients were separated into luminal A+B, HER2 enriched/overexpressed (HER2+), and triple- negative, on the basis of their staining characteristics, via conventional staining methods. Immunohistochemical (IHC) staining for CXCR4 and CD8+ TILs were performed on the archival tissues from each patient. With increasing intensity of CXCR4 staining, there was a higher incidence of lymph node metastasis (p < 0.01). Similarly, there was a positive correlation between the primary tumour size, HER2+ subtype, lymphovascular invasion, and axillary lymph node involvement. Dense lymphocytic infiltration was observed in HER2+ and triple-negative patients. No correlation between CD8+ TILs in all sites and breast cancer subtypes was discovered. A reverse correlation was discovered with CD8+ TILs stained only intratumorally and CXCR4 expression. In conclusion, lymph node involvement correlates with higher CXCR4 expression in all breast cancer subtypes. Conversely, no such correlation is found with CD8+ TILs.

Cancer stem cell and embryonic development-associated molecules contribute to prognostic significance in ovarian cancer.

OBJECTIVES: Embryonic molecules and cancer stem cell signaling resemble each other, and they organize cancer modality. We hypothesized that similar immunohistochemical expressions between tumor spheroids and patients' samples compared with clinical relevance would give an important clue in patients' prognosis. METHODS: Immunohistochemical expression of c-kit, Notch1, Jagged1, and Delta1 in 50 cases of primary ovarian tumors (10 endometrioid, 10 serous, 10 mucinous adenocarcinoma, 10 borderline serous, and 10 borderline mucinous tumors) and MDAH-2774 spheroids were investigated. Results were compared in both spheroids and tumor samples with morphologic parameters (histological grade) and clinical data (age, stage, tumor size, and metastasis). RESULTS: High c-kit and Notch1 immunoreactivity was shown in spheroids, but interestingly immunoreactivity of these molecules in tumor samples was different from patients' clinicopathological characteristics. In serous carcinoma, metastasis correlated with Notch1 immunoexpression; in mucinous carcinoma, Jagged1 immunohistochemistry correlated with grade, stage, and metastasis of tumor; in borderline serous and mucinous tumors, Jagged1 correlated with high grade. Moreover, Jagged1 correlated with stage and Notch1 with size in borderline mucinous tumor. Endometrioid carcinoma statistics showed that there was a correlation between age and Notch1 expression. CONCLUSION: Notch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas; and Notch pathway, one of the most intensively studied putative therapeutic targets, may be a useful marker for cancer. Consequently, Jagged1 could be a marker for tumor grades and Notch1 as a marker for metastases.