The impact of TP53BP1 and MLH1 on metastatic capability in cases of locally advanced prostate cancer and their usefulness in clinical practice.

BACKGROUND: Lymph node (LN) metastases increase the risk of death from prostate cancer (CaP). The dysfunction of factors responsible for DNA injury detection may promote the evolution of localized primary tumors into the metastatic form. METHODS: In this study, 52 cases of CaP were analyzed. The cases were divided into groups of CaP without metastases (N0), with metastases to the LNs (N+), and metastatic LN tissue. Immunohistochemical examinations were performed with antibodies against MDC1, TP53BP1, MLH1, MSH2, MSH6, and PMS2. RESULTS: Statistical analysis showed lower nuclear expression of TP53BP1 in N+ cases than in N0 cases (P = 0.026). Nuclear TP53BP1 expression was lower in LN cases than in N+ cases (P = 0.019). Statistical analysis showed lower nuclear expression of MLH1 in N+ cases than in to N0 cases (P = 0.003). CONCLUSION: Decreased expression of both MLH1 and TP53B1 were demonstrated in N+ cases of CaP. This observation could help to determine the risk of nodal metastasis, and to select appropriate treatment modalities for patients with locally advanced CaP.

Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. RESULTS: Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001). CONCLUSIONS: In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society.