ABSTRACT
BACKGROUND: Mucinous and signet ring cell colorectal carcinoma (m/srCRC) are challenging colorectal adenocarcinoma (CRC) types with poor prognosis. This study aimed to investigate SOX11 and ALK immunohistochemical expression in the m/srCRC group, comparing the results to those of nonmucinous CRC (nmCRC) and studying their association with different clinicopathological CRC features to better understand their significance and role. Besides, the study assesses which marker has a better predictive value for clinical practice. METHODS: Tissue microarrays were prepared from 150 CRC blocks distributed equally between the m/srCRC and nmCRC groups. SOX11 and ALK immunohistochemical expressions were compared between both groups. In addition, their association with CRC clinicopathological data and survival was investigated. The Receiver Operating Characteristic (ROC) Curve analysis examined the predictive ability of SOX11 and ALK IHC expression for CRC mortality. RESULTS: Both SOX11 and ALK expression were significantly reduced in m/srCRC compared to nmCRC. SOX11 is significantly associated with other prognostic clinicopathological factors (tumor size, lymph node status, overall TNM stage, grade, lymphovascular and perineural invasion) and overall survival. SOX11 significantly positively correlates with ALK expression. Using the ROC analysis, SOX11 is superior to ALK in survival prediction. CONCLUSION: SOX11 can be used as a prognostic marker and is a suggested therapeutic target in mucinous and signet ring cell colorectal carcinoma through upregulation modulation.
ABSTRACT
Background: CDK 4/6 inhibitors with hormonal therapy are the standard first-line therapy in metastatic hormonal receptors (HR)-positive and HER2-negative breast cancer. This study aims to assess the impact of neutropenia with 1st cycle, dose reduction, HER2-low status, and other clinicopathological factors on survival outcomes with the first-line palbociclib and hormonal therapy. Patients and Methods. In this retrospective study, we recruited patients with metastatic HR-positive and HER2-negative breast cancer. Neutropenia with 1st cycle, palbociclib dose reduction in addition to different clinicopathological and survival data were checked in patients' medical records. Survival outcomes were compared according to the abovementioned factors. Results: We recruited 150 patients who received first-line palbociclib with hormonal therapy. 86% of patients developed 1st cycle neutropenia which was more common in patients with high Ki67. Dose reduction was recorded in 46.7% of patients and it was more common in patients with higher Allred scores (scores 7-8). The median progression-free survival (PFS) of the study group was 22 months. No significant difference was observed in PFS according to the 1st cycle of neutropenia or grade of neutropenia. Similarly, no difference in PFS according to palbociclib dose reduction and HER2 low status was observed. Only the Allred score and having a single site of metastasis had an independent significant relation with PFS. The median overall survival (OS) of the study group was 39 months. No significant difference was observed in OS according to the 1st cycle neutropenia, grade of neutropenia, palbociclib dose reduction, and HER2-low status. Only the Allred score and having a single site of metastasis had an independent significant relation with OS. In addition, no difference was observed in PFS and OS according to ECOG PS (2 vs. 0-1) or menopausal status. Conclusion: No significant impact of the 1st cycle neutropenia, dose reduction, having ECOG PS2, menopausal status, or HER2 low status on survival outcome was observed. Survival outcome was significantly better in patients with single metastatic sites and higher ER-Allred scores.
