PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; p < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) (p < 0.012) due to a shorter post-metastatic survival (PMS) (p < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971–4.005; p = 0.022. HR = 2.023, 95% CI 1.003–4.091; p = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy.
Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism and mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma and resected brain metastases who underwent curative treatment between 2007 and 2017 and evaluated their prognostic significance. Tissue microarrays of primary tumors and matched metastases were analyzed using the H-score method. PI3K expression was significantly higher in primary tumors (96.8 ± 57.9 vs. 43.5 ± 62.3; p = 0.003) and in stage IV adenocarcinomas (113.3 ± 56.3 vs. 61.4 ± 47.1; p = 0.043). PINK1 expression showed no significant variation across disease stages. Univariate analysis identified older age (>55 years), PI3K overexpression (HR = 7.791, 95% CI 1.718–36.432; >50 points), and PINK1 overexpression (>100 points) in primary tumors as predictors of poor overall survival (HR = 2.236, 95% CI 1.109–4.508; p = 0.025). Multivariate analysis confirmed PINK1 overexpression in primary tumors as an independent prognostic factor (HR = 4.328, 95% CI 1.264–14.814; p = 0.020). These findings suggest that PI3K and PINK1 may serve as prognostic biomarkers in lung adenocarcinoma with resected brain metastases, emphasizing the need for research on their role in tumor progression and therapeutic response.
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. The incidence of metastasis for cSCC is estimated to be around 1.2–5%. Ribosomal protein S6 (p-S6) and the p21 protein (p21) are two proteins that play central roles in other cancers. These proteins may be equally important in cSCC, and together, these could constitute a good candidate for metastasis risk assessment of these patients. We investigate the relationship of p-S6 and p21 expression with the impact on the prognosis of head and neck cSCC (cSCCHN). p-S6 and p21 expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples from 116 patients with cSCCHN and associations sought with clinical characteristics. Kaplan–Meier estimators and Cox proportional hazard regression models were also used. The expression of p-S6 was significantly inversely associated with tumor thickness, tumor size, desmoplastic growth, pathological stage, perineural invasion and tumor buds. p21 expression was significantly inversely correlated with >6 mm tumor thickness, desmoplastic growth, and perineural invasion. p-S6-negative expression significantly predicted an increased risk of nodal metastasis (HR = 2.63, 95% CI 1.51–4.54; p < 0.001). p21 expression was not found to be a significant risk factor for nodal metastasis. These findings demonstrate that p-S6-negative expression is an independent predictor of nodal metastasis. The immunohistochemical expression of p-S6 might aid in better risk stratification and management of patients with cSCCHN.
Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism and mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma and resected brain metastases treated with curative intent (2007–2017) and evaluated their prognostic significance. Tissue microarrays of primary tumors and matched metastases were analyzed using the H-score method. PI3K expression was significantly higher in primary tumors than in metastases (96.8 ± 57.9 vs. 43.5 ± 62.3; p = 0.003) and in stage IV adenocarcinomas (113.3 ± 56.3 vs. 61.4 ± 47.1; p = 0.043). PINK1 expression showed no significant variation across disease stages. Univariate analysis identified older age (>55 years), PI3K overexpression (HR = 7.791, 95% CI 1.718–36.432; >50 points), and PINK1 overexpression (>100 points) in primary tumors as predictors of poor overall survival (HR = 2.236, 95% CI 1.109–4.508; p = 0.025). Multivariate analysis confirmed PINK1 overexpression in primary tumors as an independent prognostic factor (HR = 4.328, 95% CI 1.264–14.814; p = 0.020). These findings suggest that PI3K and PINK1 may serve as prognostic biomarkers in lung adenocarcinoma with brain metastases, highlighting the need for research on their role in tumor progression and therapeutic response.