The current application of ACOSOG Z0011 trial results: Is further implementation of sentinel lymph node intra-operative histopathological examination mandatory in breast cancer patients - a single-centre analysis.

The main objective of the ACOSOG Z0011 trial was to determine the impact of abandoning complete axillary lymph node dissection (ALND) on survival of breast cancer patients with sentinel node lymph (SLN) metastasis in whom breast conserving therapy (BCT) had been performed. The aim of our study was to assess the clinical value of intra-operative histopathological examination of SLN. Our study comprised 1284 invasive breast cancer patients in whom sentinel lymph node biopsy (SLNB) was carried out. SLN intra-operative histopathological assessment was routinely performed in patients treated within the first period (07.2013-06.2014). However, the decision regarding intra-operative assessment was made by the surgeon for the patients who underwent this evaluation in the later period 07.2014-06.2015 and were submitted for BCT. BCT was performed in 72.4% of patients. In total, 316 patients (24.6%) developed SLN-metastasis. Within the period 07.2014-06.2015, SLN intra-operative microscopic evaluation was performed in 20.8% of patients submitted for BCT. ALND was omitted in 27.5% of patients demonstrating SLN metastasis, in comparison with 15.5% of the group from the previous period (p=0.0094). The proportion of patients demonstrating macrometastasis in SLN who received conservative treatment to the axilla increased from 5.4% to 23.1% (p=0.0007). The choice of SLN final histopathological assessment may allow for deferral of decision on more extensive surgery of the axilla in patients submitted for SLNB. The omission of routinely-performed SLN intra-operative histopathological evaluation has led to a statistically significant increase in the proportion of patients in whom complete ALND was avoided.

Immune checkpoints in aggressive breast cancer subtypes.

Immune checkpoints are molecules referred to inhibitory pathways in the immune system that play a pivotal role in prevention of autoimmunity and oncogenesis. The aim of the study was to evaluate expression levels of selected immune checkpoints- PD-1 (programmed cell death protein 1), and PD-L1 (programmed cell death 1 ligand 1) in breast cancer patients, suitable for breast conservation and sentinel node biopsy and determine their associations with clinicopathological factors.Expression of the genes coding for PD-1 and PD-L1 was analyzed in formalin-fixed paraffin-embedded specimens using real-time PCR. mRNA expression levels were determined using beta actin (ACTB) as an endogenous control. There was a trend towards significance between higher PD-1 and PD-L1 levels in triple negative breast cancers (p=0.1). Higher PD-L1 expression was also found in aggressive breast cancer subtypes e.g. triple negative and HER2 (human epidermal growth factor receptor 2) -positive as compared with subtypes with better prognosis such as luminal A and luminal BHER2-negative (p=0.05). There was a trend towards significance in higher PD-1 levels in triple negative and HER-2 positive breast cancers (p=0.1). A statistically significant difference was found between PD-L1 expression and tumor grade (p=0.01). Elevated PD-L1 levels were noted in G3 tumors. Immunogenicity appears to be gaining importance in triple negative and HER2-positive molecular subtypes of breast cancer, and the results in this study provide a basis for further investigation into the role of immune checkpoints in breast cancer.

Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a Polish population.

BACKGROUND: Tobacco smoking and alcohol drinking generate oxidative DNA damage and may contribute to larynx carcinogenesis. The X-ray repair cross complementing 1 (XRCC1) and excision repair cross-complementing rodent repair deficiency, complementation group 4 (ERCC4(XPF)) genes are important components of DNA excision repair systems, which repair DNA damage induced by various factors, including tobacco smoking and alcohol. AIM: To investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population. METHODS: The polymorphisms were determined by PCR-RFLP method in 253 patients with squamous cell carcinoma of the larynx and 253 sex- and age-matched controls. RESULTS: We did not find any association between the investigated polymorphisms and larynx carcinoma, dependent on either smoking or drinking status. No association was found between these polymorphisms and larynx cancer grade, stage or age at diagnosis. CONCLUSIONS: The results indicated that Arg399Gln polymorphism of XRCC1 gene and Arg415Gln polymorphism of ERCC4 gene may not be associated with smoking- and drinking-related larynx cancer in Polish population.

DNA double strand breaks repair and apoptosis induction in peripheral blood lymphocytes of head and neck cancer patients.

AIM: To evaluate the generation and repair of DNA double strand breaks (DSBs) as a critical factors that define the efficiency of radiation therapy of cancer patients. METHODS: Peripheral blood lymphocytes obtained from 18 patients with head and neck squamous cell carcinoma (HNSCC) and 18 healthy donors were studied. The efficiency of DSBs repair after genotoxic treatment with hydrogen peroxide and gamma-radiation were examined by neutral comet assay. MTT assay was used for cell viability analysis and Annexin V-FITC kit specific for kinase-3 was employed to determine apoptosis. RESULTS: Lymphocytes from HNSCC patients were sensitive to genotoxic treatment and displayed impaired DSBs repair. Finally, as a consequence of this finding we have evidenced higher rate of apoptosis induction after gamma-radiation treatment of lymphocytes from HNSCC patients than those from healthy controls. CONCLUSIONS: DSBs repair and increased apoptosis in cells of patients with head and neck cancer is relevant for efficient therapy of HNSCC.

Polymorphisms of the DNA base excision repair gene MUTYH in head and neck cancer.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) comprise about 6% of all malignant neoplasms. The major risk factors of -HNSCC are smoking and alcohol consumption. Genetic polymorphisms of DNA repair enzymes may lead to genetic instability and carcinogenesis. MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair (BER) pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine produced by reactive oxygen species (ROS). AIM: to perform a case-control study to test the association between polymorphism in the MUTYH gene: Tyr165Cys and head and neck cancer risk progression. METHODS: Genotypes were determined in DNA from peripheral blood lymphocytes of 193 patients (among them 97 subjects with precancerous hyperplastic laryngeal lesions and 96 subjects with head and neck cancer) and 140 age, sex and ethnic-matched cancer-free controls by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). RESULTS: We found an association between head and neck cancer risk and the Tyr165Tyr variant of the MUTYH gene (OR 2.18; 95% CI 1.19-3.97). For Tyr165Tyr genotype we also observed positive correlation with cancer progression assessed by tumor size (OR 4.56; 95% CI 1.60-12.95). We did not observe any correlation between Tyr165Cys polymorphism of MUTYH gene and precancerous hyperplastic laryngeal lesions risk. CONCLUSION: The Tyr165Tyr polymorphic variant of the MUTYH gene may be associated with head and neck cancer in Polish population.