Kostadinova Kunovska, Slavica

Preferred name

Official Name

Kostadinova Kunovska, Slavica

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slavica.kostadinova@medf.ukim.edu.mk

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EP778 The role of the E-cadherin/β-catenin signal transduction pathway in the prognosis of advanced stage high-grade serous ovarian/fallopian tube cancer
(BMJ Publishing Group Ltd, 2019-11)
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Introduction/Background The aim of the study was to evaluate the correlation between E-cadherin/β-catenin expression and the clinical and pathological parameters that influence the overall survival rate in patients with advanced stage high-grade serous ovarian/fallopian tube cancer Methodology We performed a retrospective cohort study on patients that underwent primary debulking surgery at the University Clinic of Gynecology and Obstetrics, University ‘Ss. Cyril and Methodius’, Skopje, Republic of North Macedonia between January 2010 and December 2015. The following disease characteristics were analyzed: age, stage, nuclear and tumor grade, lymphovascular invasion, the extent of primary debulking, platinum-based chemotherapy resistance and overall survival. Further, we analyzed the expression of E-cadherin/β-catenin by preforming immunohistochemical staining on deparaffinized and rehydrated tissue specimens with specific monoclonal antibodies. Results A total of 84 patients with primary ovarian and 9 patients with primary fallopian tube cancer met the inclusion criteria. The overall survival of patients in the analyzed cohort was 46 months (95% CI 38–53 months). The residual tumor volume after primary debulking surgery was an independent bad prognostic factor with HR=5.32 (p<0.001). The low frequency of expression as well as the weak staining for E-cadherin were independent bad prognostic factors for the survival of these patients with HR=2.7 (p=0.05) and HR=3.38 (p=0.04), respectively. The univariate analysis also identified that the low frequency of expression and weak staining for β-catenin were bad prognostic factors, but the significance was lost in the multivariate analysis. Conclusion In this study, we identified that the residual tumor volume after primary debulking surgery and the low frequency of expression and weak staining for E-cadherin were independent, statistically significant bad prognostic factors for the overall survival of patients with advanced stage high-grade serous ovarian/fallopian tube cancer. Beta catenin expression was not found to be an independent prognostic factor in the multivariate analysis.
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Recommmendations for the diagnostic algorithm in lung cancer. Consensus statement of the Macedonian respiratory society and the Macedonian association of pathology
(Македонско лекарско друштво = Macedonian Medical Association, 2019)
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Todevski Dejan
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Rexhepi Arben
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Tatabitovska Aleksandra
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Lung cancer is the “number one cancer killer” in the world. Its prevalence is associated to smoking as the primary cause, although air pollution in general and genetic factors are also in stake. The mortality especially from advanced stage lung cancer is still high, although there has been a significant improvement in the past 10 years, mostly due to the introduction of novel compounds such as targeted and immunological treatment. The advances in the treatment of NSCLC have imposed updating of the guidelines for the diagnostic procedure and screening of LC, for the indications for molecular testing as well as for targeted selection of patients who shall benefit the most of the novel treatment modalities. These recommendations shall fulfill their purpose only if implemented in the educational curriculum and if incorporated in the healthcare system strategies.
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Standardization and optimization of fluorescence in situ hybridization (FISH) for HER-2 assessment in breast cancer: A single center experience
(Association of Basic Medical Sciences of FBIH, 2018-05-20)
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<jats:p>Accurate assessment of human epidermal growth factor receptor 2 (HER-2) is crucial in selecting patients for targeted therapy. Commonly used methods for HER-2 testing are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Here we presented the implementation, optimization and standardization of two FISH protocols using breast cancer samples and assessed the impact of pre-analytical and analytical factors on HER-2 testing. Formalin fixed paraffin embedded (FFPE) tissue samples from 70 breast cancer patients were tested for HER-2 using PathVysion™ HER-2 DNA Probe Kit and two different paraffin pretreatment kits, Vysis/Abbott Paraffin Pretreatment Reagent Kit (40 samples) and DAKO Histology FISH Accessory Kit (30 samples). The concordance between FISH and IHC results was determined. Pre-analytical and analytical factors (i.e., fixation, baking, digestion, and post-hybridization washing) affected the efficiency and quality of hybridization. The overall hybridization success in our study was 98.6% (69/70); the failure rate was 1.4%. The DAKO pretreatment kit was more time-efficient and resulted in more uniform signals that were easier to interpret, compared to the Vysis/Abbott kit. The overall concordance between IHC and FISH was 84.06%, kappa coefficient 0.5976 (p < 0.0001). The greatest discordance (82%) between IHC and FISH was observed in IHC 2+ group. A standardized FISH protocol for HER-2 assessment, with high hybridization efficiency, is necessary due to variability in tissue processing and individual tissue characteristics. Differences in the pre-analytical and analytical steps can affect the hybridization quality and efficiency. The use of DAKO pretreatment kit is time-saving and cost-effective.</jats:p>
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Low-grade malignancy glomus tumor of the abdominal wall: a case report and literature review
(Oxford University Press (OUP), 2023-12)
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Gelevski, Radomir
Glomus tumors are painful neoplasms arising from the glomus body (responsible for body temperature and blood pressure regulation) in the skin. Although mostly present in the interdigital areas, glomus tumors can arise elsewhere. The vast majority of them are benign. Rarely, malignant variants are reported and are associated with the potential for local infiltration and metastatic dissemination. The abdominal wall location of glomus tumors is extremely rare regardless of whether they present as benign or malignant. We present a case of a 58-year-old female patient with a low-grade malignancy infiltrative glomus tumor of the abdominal wall.
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Pigmented papillary carcinoma of male nipple mimicking melanoma
(Springer, 2021-08-31)
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Background and objective: Primary melanomas of breast and carcinomas with pigment rich melanocytes are well known entities. Melanoma in nipple-areola complex is extremely rare and in differential diagnosis must be distinguished between Paget disease, melanoma from extramammary sites and other invasive carcinomas. We present a case of invasive papillary carcinoma of male nipple with melanin laden tumor cells. Methods: A 71-year old male patient presents with lobulated grayish tumor of the right nipple measuring 2x1, 3 cm elevated above the skin surface 1cm. The lesion was surgically removed with skin excision 0,7x 0,5x 0,5cm. The specimen was formalin-fixed and paraffin-embedded, routinely stained with HE. Additional immunohistochemical analysis was performed with CK7, ER, SMA, S-100, and Melan A. Results: The gross specimen on cut sections revealed solid white to brown tumor, well demarcated at the base and ulceration of overlying epidermis. Histomorphology of the sections showed papillary structures with tall columnar cells overlying fibrovascular cores, as well as micropapillary formations. There were areas of solid and cribriform growth pattern. Microcalcifications were diffusely present. There were accumulated melanophages in subepithelial tissue and melanin granules were also found in tumor cells. Immunohistochemical analysis showed that tumor cells were positive for CK7, with strong and diffuse nuclear stain for ER, with complete absence of myoepithelial cell on SMA stain. Melan A and S-100 were negative. Although rare, a diagnosis of pigmented papillary carcinoma was made. Conclusion: Pigmented carcinomas of breast are rare. When they are localized in areolar region the diagnosis should be carefully made to exclude lesions with melanocytic differentiation. The pigmentation should be considered also as a result by proximity to epidermis. The distinction between benign and malignant papillary lesions is quite difficult in most cases. The prognosis of patients with papillary carcinoma is relatively favorable.
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Prenatal Diagnosis of Cryptic Translocation t(5p;17q) with Fluorescent In Situ Hybridization
(Springer Science and Business Media LLC, 2018-03-08)
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E. Sukarova-Stefanovska
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G. Ilieva
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T. Hristova-Dimkovska
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Consensus statement: RECOMMENDATIONS FOR THE DIAGNOSTIC ALGORITHM IN LUNG CANCER CONSENSUS STATEMENT OF THE MACEDONIAN RESPIRATORY SOCIETY AND THE MACEDONIAN ASSOCIATION OF PATHOLOGY
(Македонско лекарско друштво = Macedonian Medical Association, 2019)
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Dejan Todevski
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Arben Rexhepi
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Aleksandra Tatabitovska
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Lung cancer is the “number one cancer killer” in the world. Its prevalence is associated with smoking as the primary cause, although air pollution in general and genetic factors are also important. The mortality especially from advanced stage lung cancer is still high, although there has been a significant improvement in the past 10 years, mostly due to the introduction of novel compounds such as targeted and immunological treatment. The advances in the treatment of NSCLC have imposed updating of the guidelines for the diagnostic procedure and screening of LC, for the indications for molecular testing as well as for targeted selection of patients who shall benefit the most from the novel treatment modalities. These recommendations shall fulfil their purpose only if implemented in the educational curriculum and if incorporated in the healthcare system strategies.
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Novel Ret Mutations in Macedonian Patients with Medullary Thyroid Carcinoma: Genotype-Phenotype Correlations
(Walter de Gruyter GmbH / MANU, 2015-05-01)
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Bogoeva, Biljana
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Medullary thyroid carcinomas (MTCs) are rare neoplasms comprising 2-10% of all thyroid malignnancies. More than 75% are sporadic tumors and the remainder is familial and MEN2 related. Both sporadic and syndromic MTCs frequently show mutations in the RET proto-oncogene. It has been noted that some MTC cases present an indolent, and some an aggressive clinical course. Ki-67 expression is generally low, with documented exceptions, whereas high expression of Bcl-2 has been reported in majority of the cases. Some studies have shown that Ki-67 and Bcl-2 expressions have prognostic value, as well as RET mutational status. We analyzed 20 unrelated MTC cases for Ki-67, Bcl-2 expression and RET mutations and tested their intercorrelations, correlations to the morphologic features and stage of the tumors, as well as their influence on survival. In 13 of the 20 analyzed cases we found 23 sequence changes distributed in exons 8, 10-13 and 16. There were 11 different missense mutations, single nucleotide deletion with frameshift, and 8 different synonymous mutations. Only 4 of the sequence changes have been previously published. Twelve patients (60%) had tumors expressing one or more missense mutations or single nucleotide deletion and 7 of them (35%) had at least one damaging or possibly damaging RET mutation. Most of the tumors had low Ki-67 expression (mean 6.48% of cells) and high Bcl-2 expression (mean 68.3%). Significantly better survival was observed in cases with low Ki-67 (< 6.5%; p < 0.05), high Bcl-2 expression (> 68.3%; p < 0.01) and younger age at diagnosis (< 51 years; p < 0.05).
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The Evaluation of Sentinel Lymph Node Biopsy Using Radiocolloid in First Stage Endometrial Cancer
(Galenos Yayinevi, 2023-06-20)
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Stojchevski, Sasho
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Detection of a sentinel lymph node (SLN) in patients with endometrial cancer (EC) reduces the rate of unnecessary systemic lymph dissection. The aim of this study was to assess the SLN detection rate, accuracy of the method using Tc-99m-SENTI-SCINT and the rate of metastatic nodal involvement in patients with preoperative first stage EC.
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Thyroid cancer detection rate and associated risk factors in patients with thyroid nodules classified as Bethesda category III
(Walter de Gruyter GmbH, 2018)
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Background Ultrasound guided fine-needle aspiration (FNA) is a standard procedure for thyroid nodules management and selecting patients for surgical treatment. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), as stated by The Bethesda System for Reporting Thyroid Cytopathology, is a diagnostic category with an implied malignancy risk of 5-15%. The aim of our study was to review cytology and histopathology reports, as well as clinical and ultrasound data, for thyroid nodules reported as AUS/FLUS, in order to evaluate the malignancy rate and to assess factors associated with malignant outcome. Patients and methods A total of 112 AUS/FLUS thyroid nodules in 105 patients were evaluated, of which 85 (75.9%) were referred to surgery, 21 (18.8%) were followed-up by repeat FNA and 6 nodules (5.3%) were clinically observed. Each was categorized in two final diagnostic groups - benign or malignant, which were further compared to clinical data of patients and ultrasonographic features of the nodules. Results Final diagnosis of malignancy was reached in 35 cases (31.2%) and 77 (68.8%) had benign lesions. The most frequent type of cancer was papillary thyroid carcinoma (PTC) - 58.1% PTC and 25.8% had follicular variant of PTC. Patients' younger age, smaller nodule size, hypoechoic nodule and presence of calcifications were shown to be statistically significant risk factors for malignancy. Conclusions The rate of malignancy for the AUS/FLUS diagnostic category in our study was higher than estimated by the Bethesda System. Clinical and ultrasound factors should be considered when decision for patient treatment is being made.

Kostadinova Kunovska, Slavica

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