Tumor-infiltrating lymphocytes and levels of PD-L1 and BRCA protein expression may identify patients with breast cancer with a higher rate of BRCA1 mutations

Background & objectives Breast cancer (BC) is a heterogeneous disease, treated as per the predictive role of immunohistochemistry (IHC) identifiers as estrogen / progesterone and HER2 receptor proteins. Deeper molecular classification (MC) identifies molecular subtypes according to the gene-expression profiles with different molecular genetic alterations and biological features, present in the different subtype. Overlap between IHC and MC exists, though incomplete. We aimed to identify overlap between IHC and MC and identify patients with basal-like subtype of BC. We hypothesized that the rates of the tumor expression of breast cancer 1 (BRCA1) protein, the type of tumor-infiltrating lymphocytes and the expression of programmed death ligand 1 (PD-L1) by immune cells may be incorporated in a prognostic algorithm to predict morphological screening, identifying patients with potentially altered BRCA1 gene activity. Methods Parafin-embedded samples from 100 patients with primary invasive BC were analyzed and expression levels estrogen and progesterone receptors, HER2 status and Ki-67 were assessed via IHC, defining four groups - Luminal A-like, Luminal B-like, HER2 positive non-luminal and triple negative (TN). The primary endpoint of our study was to identify via IHC with CK 5/6 and 17 basal-like subtype of BC amongst others and to describe specific clinicopathological features together with protein expression of BRCA1 and PD-L1 and tumor-infiltrating lymphocytes, using CD20, CD3, CD4, CD8 and FoxP3. Results Basal-like BC were predominantly characterized as triple negative by IHC (p < 0.05) and were more frequently seen among special BC ductal subtypes as compared to no special type (NST) with (p=0.036). Their immune response was represented mostly by high concentration of intratumoral cytotoxic CD8+ T-lymphocytes (p < 0.05) and stromal PD-L1 positive immune cells (p=0.008). In these tumors, absence of expression of BRCA1 protein was more frequent (p < 0.001). Basal-like subtype of BC with absent expression of BRCA1 is associated with worse < 5-year survival (p=0.001 and p=0.017, respectively). Conclusion The established dependencies can be, allowing better selection of patients with BC for subsequent genetic analysis of BRCA1 gene and for application of appropriate therapy

Tumor-infiltrating lymphocytes and levels of PD-L1 and BRCA protein expression may identify patients with breast cancer with a higher rate of BRCA1 mutations

Introduction.Breast cancer (BC) is a heterogeneous disease, treated as per the predictive role of immunohistoche­mistry (IHC) identifiers as estrogen/progesterone and HER2 receptor proteins. Deeper molecular classification (MC) identifies molecular subtypes according to the gene-expression profiles, with different molecular genetic alterations and biological features, present in the different subtype. An overlap between IHC and MC exists, even if somewhat incomplete. We aimed to identify the overlap between IHC and MC, and identify patients with basal-like subtype of BC. We hypothesized that the rates of tumor expression of breast cancer-related protein 1 (BRCA1), the type of tumor-infiltrating lymphocytes, and the expression of programmed death ligand 1 (PD-L1) by immune cells vary among different subtypes of BC. Material and methods.Parafin-embedded samples from 100 patients with primary invasive BC were analyzed and expression levels of estrogen and progesterone receptors, HER2 status, and Ki-67 were assessed via IHC, defining four groups – luminal A-like, luminal B-like (LumA, LumB), HER2-positive non-luminal, and triple negative (TN). The pri­mary endpoint of our study was to identify via IHC with CK5/6 and 17 basal-like subtypes of BC amongst others, and to describe specific clinicopathological features together with protein expression of BRCA1 and PD-L1 and tumor-infiltrating lymphocytes, using CD20, CD3, CD4, CD8, and FoxP3. Results.Basal-like BC were predominantly characterized as triple negative by IHC (p < 0.05) and were more frequently seen among special BC subtypes as compared to no special type (NST), with p = 0.036. Their immune response was represented mostly by high concentration of intratumoral cytotoxic CD8 (+) T-lymphocytes (p < 0.05) and stromal PD-L1-positive immune cells (p = 0.008). In these tumors, absence of expression of BRCA1 protein was more frequent (p < 0.001). Basal-like subtype of BC with absent expression of BRCA1 is associated with poorer <5-year survival (p = 0.001 and p = 0.017, respectively). Conclusions.The use of IHC can establish basal-like BC, the type of its immune response and possible dysfunction in the BRCA-gene, reflected in the lack of expression in the BRCA-related protein

Endometriosis and risk of ovarian cancer

Endometriosis is common in premenopausal women and affects about 10% of women of reproductive age. It is a benign condition but demonstrates malignant behaviour with recurrences and metastases. Its tendency to increase the risk of specific subtypes of ovarian cancer is being discussed, because they exhibit specific clinical features that distinguish them from classical ovarian cancer. Malignant transformation of endometriosis goes through its transition to atypical endometriosis. Although endometriosis-associated ovarian carcinomas have a good prognosis, adequate follow-up and monitoring after treatment of endometriosis are recommended

Two relatives female patients with primary malignant phyllodes sarcoma and primary stromal sarcoma of breast

The primary sarcoma of breast is a rare malignant tumor, which develops from the mesenchymal tissue of mammary gland. It represents less than 1% of all malignant diseases of breast. The incidence is about 17 new cases per 1 000 000 women. The etiology of that disease is unknown. The main method of treatment is the surgical excision with includes ";;;;safety-margin";;;; of healthy-looking tissues. We present a 57-year-old woman with probably familial, primary, malignat phyllodes sarcoma

Endometrial carcinoma in patients under 40 years of age: insights from the bulgarian cancer registry

Objectives: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. Material and methods: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. Results: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. Conclusions: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization

Endometrial carcinoma in patients under 40 years of age : insights from the Bulgarian cancer registry

Objectives: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival.Material and methods: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification.Results: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%.Conclusions: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.peer-reviewe

Pudendal nerve block as a countermeasure to postoperative chronic pain after removal of Bartholin's cyst

The chronic pain syndrome is a serious post-operative complication. In our practice we have discovered a certain percent of neuralgia of the pudendal nerve in vaginal surgery – more precisely in Bartholin’s cyst removal. As a highly efficient countermeasure we propose a nerve block of the pudendal nerve. We have performed a retrospective study of patients who underwent a Bartholin’s cyst removal in the span of 1 year from January 1st 2019 to December 31st 2019. All of the patients included are diagnosed with chronic pain in the area innervated from the pudendal nerve. In all of the patients a pudendal nerve block with local anesthetic was performed under the guidance of ultrasound. A total of 11 patients were included in the study. There was a time interval between the Bartholin’s cyst removal surgery and the performance of the nerve block. All patients expressed moderate pain before the procedure. In only 1 case a repeat of the nerve block was imposed. There were no short- or long-term complications of any kind. The patients have been followed-up in the duration of 1 year and 100% has been reported. Accurate and precise pain assessment is vital of the diagnosing and subsequent treatment of the chronic pain syndrome. There are many ways of treating the syndrome both conventional (non-steroidal anti-inflammatory drugs, opioids, topical analgesics and adjuvant analgesics) and unconventional. Chronic pain syndrome is an important multilayered problem that requires personal approach. The nerve block of the pudendal nerve is a highly efficient method of coping with that disease