Prospects of POLD1 in Human Cancers: A Review.

Cancer is the second leading cause of death globally, exceeded only by cardiovascular disease. Despite the introduction of several survival-prolonging treatment modalities, including targeted therapy and immunotherapy, the overall prognosis for the metastatic disease remains challenging. Therefore, the identification of new molecular biomarkers and therapeutic targets related to cancer diagnosis and prognosis is of paramount importance. DNA polymerase delta 1 (POLD1), a catalytic and proofreading subunit of the DNA polymerase δ complex, performs a crucial role in DNA replication and repair processes. Recently, germline and somatic mutations of the POLD1 gene have been acknowledged in several malignancies. Moreover, diversified POLD1 expression profiles have been reported in association with clinicopathological features in a variety of tumor types. With this review, we aim to summarize the current knowledge on the role of POLD1 in cancers. In addition, we discuss the future prospects and clinical applications of the assessment of POLD1 mutation and expression patterns in tumors.

Altered immunoexpression of DNA polymerase delta 1 catalytic subunit (POLD1) in colorectal cancer.

Introduction: The study aimed to determine the immunoexpression levels of polymerase delta 1 catalytic subunit (POLD1), a catalytic and proofreading subunit of DNA polymerase delta, in the sections of colorectal cancer (CRC), and to evaluate the significance of POLD1 as a potential prognostic factor in CRC. Material and methods: Paired, tumour and non-cancerous tissue samples of the large intestine distant to the neoplasm were collected from the postoperative material of 78 patients who underwent surgical resection of CRC tumours. Polymerase delta 1 catalytic subunit protein levels were determined using immunohistochemistry. Clinical, pathomorphological, and survival data of the patients were pooled. In addition, POLD1 mRNA expression levels of 599 CRC patients were extracted from The Cancer Genome Atlas (TCGA) datasets and subjected to statistical and survival analysis including the Kaplan-Meier method followed by the log-rank test. Results: Immunoexpression of POLD1 was found in the nuclei of the tumour cells and epithelial cells of unchanged intestinal mucosa. Polymerase delta 1 catalytic subunit immunoreactivity in the tumour was heterogenous, and the average immunoreactivity score was decreased in cancer cells when compared to the mucosa of matched sections of unchanged large intestine (p = 0.0259). However, POLD1 expression at the protein and mRNA levels did not associate with clinicopathological characteristics of the patients and their survival. Conclusions: Despite previous studies suggesting that POLD1 genetic alterations could be promising molecular biomarkers in CRC, our results do not support any prognostic significance of POLD1 expression in CRC.

DNA Polymerase Delta 1 Catalytic Subunit (POLD1) as a Prognostic Factor in Clear Cell Renal Cell Carcinoma Patients.

BACKGROUND/AIM: DNA polymerase delta 1 catalytic subunit (POLD1 or POLD1/p125) plays a crucial role in DNA synthesis and proofreading during the semiconservative genome replication. Mutations of POLD1 are associated with abnormal cell division in various human tumors. However, the significance of altered POLD1 expression in malignant diseases and its usefulness as a prognostic factor is not fully understood. This study aimed to determine POLD1 immunoexpression levels in paired sections of tumor and normal kidney derived from 56 patients with clear cell renal cell carcinoma (ccRCC) and evaluate the significance of POLD1 protein as a potential prognostic factor in ccRCC. MATERIALS AND METHODS: Tissue samples were collected from 56 patients (27 females and 29 males, mean age 62.6, range=27-83 years) who underwent nephrectomy due to ccRCC. Paired tissue samples were obtained from the tumor and unchanged part of the kidney. The expression of POLD1 protein was assessed by immunohistochemistry. Clinical and pathological data of patients were also collected. Patients were followed-up and the median time of observation period was 39.3 months. RESULTS: The study revealed a significantly higher POLD1 nuclear expression in ccRCC tumor tissue samples and this was correlated with longer survival rates (better prognosis) of ccRCC patients. CONCLUSION: POLD1 immunoreactivity in ccRCC postoperative material could be helpful as a prognostic marker in the ccRCC patient group.

Cancer in a polyp of the large intestine - an interdisciplinary decision problem.

Large intestine polyps are commonly found during colonoscopies. Pedunculated colon polyps can be totally removed using an endoscopic invasive technique. A problem arises when the pendulated polyp contains cancerous infiltration. The aim of the article was a presentation of the clinical decision process concerned with the presence of cancer invasion tissue within colorectal polyps. Review of literature source and presentation of histological sample photography. A correct interpretation of the pathomorphological protocol is crucial for the therapeutic decision, which should be consistent with the actual recommendations of gastroenterological societies. Local treatment is considered as complete when the adenocarcinoma is well or moderately differentiated without any microinvasion of blood and lymphatic vessels and the resection margin is more than 1 mm from the cancer tissue infiltration. In the contemporary clinical practice patients with a colon polyp require rational clinical decisions, which are based on the actual recommendations.

Recanalization and remodeling of the great saphenous vein caused by the large melanoma's cutaneous metastasis.

AIM OF THE STUDY: Large melanoma tumour caused arterial remodelling of the distal part of the great saphenous vein. The metastasis occurred at the site where inguinal lymphadenectomy was previously performed and the proximal part of the great saphenous vein was resected.The aim of this study is the presentation of such a rare observation and literature overview concerning melanoma metastasis and possible stimuli causing remodelling of veins. MATERIAL AND METHODS: Macroscopic and microscopic analyses of the large blood vessel that supplies melanoma were made. The size and structure of the blood vessel was compared with the regular great saphenous vein. RESULTS: The macroscopic examinations allowed us to ascertain that the blood vessel that was identified intraoperatively as the great saphenous vein, has a thick, stiff wall. The microscopic analysis allowed demonstrated that the tunica media was typical for a muscular artery morphology. The morphometric analysis revealed that the blood vessel wall in the area of metastatic tumour was much thicker than the wall of a regular great saphenous vein. CONCLUSIONS: This malignant melanoma skin metastases caused the recanalisation of the great saphenous vein the lumen of which was obliterated during the initial surgical treatment. The metastatic tumour supplied by large blood vessels grew extensively and caused arterial remodelling of the venous wall.