Wioletta Pietruszewska

Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

BackgroundThe genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of XRCC1 gene with human head and neck squamous cell carcinoma (HNSCC).MethodsThe genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease Msp I.ResultsNo altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80).ConclusionFinally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene XRCC1 that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.

Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population

Genetic variations in DNA repair genes may affect an individuals susceptibility to head and neck cancer. We performed a case-control study to test the association between head and neck cancer risk and two polymorphisms: the C722T of the XRCC3 and the G135C of the RAD51-genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02-14.74) as well as 722TT (OR 4.65; 95% CI 2.30-9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61-4.16 and OR 5.54; 95% CI 3.22-9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69-9.90) and HNSCC (OR 6.04; 95% CI 3.69-9.90) and the 135GC variant of the RAD51 gene. The gene-gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55-9.75) as well as the 722TT/135GC genotypes (OR 5.33; 95% CI 1.96-14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22-4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69-7.76 for 722TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85-10.28 and 1.82-7.35, respectively) and HNSCC patients (ORs 2.94-13.93 and 1.36-3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44-6.12 and 3.52-8.43, respectively) and HNSCC subjects (ORs 2.71-7.01 and 2.33-4.62, respectively). In conclusion our data showed that the C722T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population.

MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study.

In the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR-restriction fragment lenght polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19–2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07–10.05) variants of the OGG1 gene. The gene–gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25–3.11), (OR 3.54; 95% CI 1.39–9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non-smoking status in HNSCC (OR 0.34; 95% CI 0.17–0.66). We also found a link between gene–gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17–4.20 and 2.18–5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population.

Recommendations for the diagnosis of human papilloma virus (HPV) high and low risk in the prevention and treatment of diseases of the oral cavity, pharynx and larynx. Guide of experts PTORL and KIDL

The role of human papilloma viruses (HPV) in malignant and nonmalignant ENT diseases and the corresponding epidemiological burden has been widely described. International head and neck oncology community discussed growing evidence that oral HPV infection contributes to the risk of oro-pharyngeal carcinoma (OPC) and recommended HPV testing as a part of the work up for patients with OPC. Polish Society of ENT Head Neck Surgery and National Chamber of Laboratory Diagnosticians have worked together to define the minimum requirements for assigning a diagnosis of HPV-related conditions and testing strategy that include HPV specific tests in our country. This paper briefly frames the literature information concerning low risk (LR) and high risk (HR) HPV, reviews the epidemiology, general guidance on the most appropriate biomarkers for clinical assessment of HPV. The definition of HPV-related cancer was presented. The article is aiming to highlight some of major issues for the clinician dealing with patients with HPV-related morbidities and to introduce the diagnostic algorithm in Poland.

Amyloidosis of the head and neck: a clinicopathological study of cases with long-term follow-up

Extracellular deposits of insoluble proteinaceous material giving a starch-like reaction when treated with iodine and sulphuric acid and accumulating in tissue was for the first time described by Rokitansky in 1842 [1]. It was not until 1851 that Virchow applied the term “amyloidosis” to describe this deposition [2]. An amorphous substance called amyloid (insoluble fibril-forming protein) is deposited in extracellular spaces of organs and tissues. Amyloid deposits, under the electron microscope, appear as non-branching fibrils with a cross-linked, β-pleated sheet conformation. They are eosinophilic after haematoxylin–eosin staining and display apple-green birefringence with polarized light when stained with Congo red. Chronic inflammations of bacterial or non-bacterial origin and immunological immune-competent neoplasm cells are examples of factors that induce amyloid fibril biosynthesis. The organs and tissues where amyloid deposits occur become stiff and plastic, having a hyaline-like appearance that leads to a loss of previous function [3].

The content of cadmium, cobalt and nickel in laryngeal carcinoma.

Introduction The aim of the study was to determine the content of cadmium (Cd), cobalt (Co) and nickel (Ni) in the samples from laryngeal carcinoma in comparison with the level of these elements in the samples of healthy mucous membrane from the same larynx. Material and methods The study was conducted on 43 patients with laryngeal carcinoma. The levels of Cd, Co, and Ni in carcinoma and healthy control tissues was determined by inductively coupled plasma optical emission spectrometry (ICP – OES) using sequential spectrometer. Results No significant differences were found between the levels of the Cd, Co, and Ni in laryngeal carcinoma vs tissues without carcinoma. However, it was noted that the concentration of Cd in tumors of patients with metastases to cervical lymph nodes was significantly higher than in tumors without metastases. The content of Co was significantly higher in more advanced laryngeal tumors: in stage-T4 than in stage T3. It is of interest that the levels of Cd, Co and Ni were significantly higher in tumors in patients from rural than urban areas. Conclusions The imbalance in the level of nickel, cadmium and cobalt in laryngeal cancer may be due to a changed cellular metabolism in the cancer process. However, the results of our study reveal the significant differences in the concentration of these metals between patients from urban and rural areas which suggests that this fact may be related to environmental or occupational factors and therefore it requires further study.

Application of primary cell cultures of laryngeal carcinoma and laser scanning cytometry in the evaluation of tumor reactivity to cisplatinum

Unsatisfactory effects of treatment of laryngeal carcinoma patients stimulate the clinicians as well as researchers to develop new more effective treatment models and to find new reliable prognostic factors. The aim of the present study was the evaluation of the use of primary cell cultures of the laryngeal carcinoma and laser scanning cytometry (LSC) in the assessment of tumor reactivity to cisplatinum. Nineteen primary cultures of laryngeal carcinoma cells established from fragments of laryngeal carcinoma infiltrations were cultured with or without cisplatin, stained with monoclonal antibodies against P53 and BCL-2 proteins and analyzed by LSC. Cisplatin added to the culture medium leads to the significant increase of P53 expression and decrease of BCL-2 expression. Moreover, changes of P53 and BCL-2 expressions were significantly correlated. Our findings of apoptosis regulatory mechanisms could be useful in patient qualification for the chemotherapeutic follow-up treatment.

Papillary carcinoma in thyroglossal duct cyst with uninvolved thyroid. Case report and review of the literature

The thyroid gland in embryogenesis develops as the first pharyngeal derivative, primarily appearing as an invagination in the floor of the pharynx and then migrating caudally to the trachea. During embryogenic development, it remains attached to the tongue by the thyroglossal duct, which usually undergoes atrophy after birth. If it fails to involute, it can persist as a cyst, a duct, or ectopic tissue, which is localized in the midline between the base of the tongue and the pyramidal lobe of the thyroid gland [1].

Analiza ekspresji TIMP-1, TIMP-2 i TIMP-3 jako czynnika prognostycznego przebiegu raka krtani ☆ ☆☆

Summary Introduction Tissue inhibitors of matrix metalloproteinases (TIMPs) are natural regulator of activity of matrix metalloproteinases, that are responsible for ECM degradation. TIMPs have been identified in various carcinomas and in most of them dependence between TIMPs and clinical course of the disease have been observed. Aim Of the research was to evaluate expression of TIMP-1, TIMP-2 and TIMP-3 in laryngeal cancer and to asses the prognostic significance of these factors. Material and method 104 patients with laryngeal cancer, that underwent surgical treatment were included in the study. Only cases with at least a 5-year follow-up were included. Immunohistochemical studies were performed on formalin fixed, paraffin embedded sections by using monoclonal antibodies against TIMP-1, -2 and -3 antigens and ABC detection system. Results TIMPs expression was cytoplasmatic, mainly in cancer cells, but also in some stromal cells. TIMP-1 and TIMP-2 correlated with grading (TIMP-1 p = 0,05; TIMP-2 p = 0,001). There was an association between TIMP-2 and TIMP-3 expression and tumor size (TIMP-2 p = 0,037; TIMP-3 p = 0,022). TIMP-3 expression correlated with clinical stage of the disease (p = 0,037). There was an association between TIMP-2 expression and nodal recurrence (p = 0,05). Both overall and disease-free survival were shorter in cases with positive TIMP-2 expression (p = 0,049). Conclusions Our results demonstrate that there is an association between TIMPs expression and clinicopathological features of laryngeal cancer. Moreover TIMP-2 could be an important marker in prognosis of laryngeal cancer patients.

Angiofibroma jamy nosa i komórek sitowych przednich u kobiety – problemy diagnostyki różnicowej ☆ ☆☆

Summary Background Nasal angiofibromas are commonly called juvenile nasal angiofibromas (JNA) because of the almost exclusive occurrence in adolescent males. It is a relatively rare benign fibrovascular tumor originating in the posterior lateral wall of the nasopharynx with only a very few cases diagnosed in females. Case report Authors present a case of a 26 y.o. woman with JNA in left nasal cavity with extension to the anterior left ethmoid cells diagnosed and surgically treated at the ENT Department, Medical University of Lodz. Patient presented in past medical history: lymphoma malignum – abdominal location – surgical treatment and chemotherapy (1986) with no clinical signs of recurrence. Diagnosis based on histopathologic examination with immunochemical staining (vimentin, actin, desmin, S–100 protein). CT of paranasal sinuses in frontal and axial plains – left nasal cavity filled with a solid pathologic tissue. In the left anterior ethmoid cells extension of the tumor could be seen. Surgical treatment – tumor has been surgically resected with no complications. In a 12 month follow up patient shows no signs of recurrence. Conclusion Although angiofibroma in females is an extremely rare tumor of a sinonasal tract it should be taken into consideration in the differential diagnosis of all nasal cavity tumors (especially solitary fibrous tumor). It is not possible to make differential diagnosis on physical examination. The only way to confirm the diagnosis is histopathologic examination with immunochemical staining.