Faculty of Medicine

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Детекција на ИгМ и ИгГ антитела на токсоплазмоза кај пациенти со ХИВ инфекција
(1999)
Стојоска П
;
Каламарис Р
;
Јовановска Д
;
;
Стојковски З
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Predictive value of estrogen receptors evaluated by immunocytochemical analysis in breast cancer patients
(Gustav Fischer, 1997-09)
Yashar, Genghis
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Ivkovski, Ljube
;
;
Zografski, George
BACKGROUND: The determination of estrogen receptor (ER)status is valuable in selecting the appropriate therapy and predicting prognosis for patients with invasive breast carcinoma. OBJECTIVE: The aim of our study was to assess the predictive value of ER status evaluated preoperatively by immunocytochemical analysis and compared with recurrence rate, clinical and histopathological features in 52 patients with breast carcinoma. MATERIALS AND METHODS: Fifty-two aspirates obtained by fine-needle-aspiration biopsy (FNAB) were prepared as cytospin samples for ER-immunocytochemical analysis (ER-1CA). Cytospin slides were stained using a standard procedure with horseradish peroxidase-antiperoxidase (PAP) method, utilising monoclonal antibody to ER (H222SP, ER-ICA kit, Abbott Laboratories, USA). The assessment of staining was scored in a semiquantitative fashion incorporating the intensity and the distribution of stained cells and the values were designated as IS-CYTOSCORE. All the patients underwent radical mastectomy with axillar lymphadenectomy during the period from September 1990 to March 1992 and were staged according to the postoperative pTNM classification of UICC (1987) guidelines. During the follow-up period (range, 2-75 months, mean 32) recurrences were observed in 25 (48%) patients.ER status was correlated to recurrence rate, age of the patients, type of the breast carcinoma, tumor size, grade of histologic differentiation, desmoplastic reaction, elastosis, necrosis and calcifications. The comparison was made by cross-classification and statistical significance determined by χ2 and Fisher's exact test. RESULTS: ER status was positively detected in 28 (53.8%) patients. There is significant association between ER status and age of the patients (p = 0.02), the type of the breast carcinoma (p = 0.018), and the recurrence rate (p = 0.012). Eighteen out of 26 (70%) patients 50 years or older, were positively related to ER status. In 22 (42.3%) lobular carcinomas, ER status was positive in 16 (73%) patients, compared with 30 (57.7%) ductal carcinomas, with ER status positive for 12 (40%) patients, only. Recurrences were observed in 16 (64%) patients with ER- breast carcinomas and 9 (36%) patients with ER+ breast carcinomas. Less important histopathological features as elastosis and calcifications, demonstrated statistically significant positive relation with ER status (p = 0.004 and p = 0.005, respectively). No significant association was found between the ER status and other histopathological characteristics. CONCLUSION: Our results suggest that recurrences, age of the patients and the lobular type of breast carcinoma are positively correlated with ER status. These data are consistent with the results of other similar studies. On the other hand, the stage of the disease as well as the grade of histologic differentiation and lymph node involvement, demonstrated no significant association with ER status as expected. A small number of cases studied and the heterogeneous stages included, could explain some of the differences between our data and the results from other studies. Semiquantitative ER-1CA, as fast and simple method, is especially useful in determination of ER status in recurrent, metastatic and small-sized breast carcinomas. The great advantage of ER-ICA is in a possibility of ER status preoperative determination, and repeating the procedure, if necessary. Despite the good performances, some inherent difficulties must be noted: subjectivity in scoring and detection by antigenicity of ER. Therefore, ER status quantitative assessment by using Cell-Analysing-System (CAS) and concomitant quantitative measurements of progesterone receptor status, should be of additional benefit.
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Human papilloma virus DNA presence in early stage cervical carcinomas: Correlation with other prognostic factors and recurrence rate
(Gustav Fischer, 1997-09)
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Ivkovski, Ljube
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Yashar, Genghis
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Stavrik, George
BACKGROUND: Although the role of human papillomavirus (HPV) in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. OBJECTIVE: The objective of our study was to assess the prognostic significance of the presence of HPV DNA by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 92 patients with cervical carcinoma..In this report the preliminary results of a larger programme aimed to search for the prognostic factors in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy, followed by postoperative adjuvant pelvic radiotherapy, are presented MATERIALS AND METHODS: Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51 (Enzo Diagnostics, New York). Clinical data and histopathologic features of these patients were analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 48 (52.2%) patients, while local extension to vagina and parametrial tissues was found in 10 (10.9%) and 34 (36.9%) patients, respectively. Pelvic lymph node involvement was found in 25 (27.2%) patients. During the follow-up period (range, 2-87, mean, 35 months), recurrences were observed in 13 patients. Variables were compared by cross-classification and statistical significance was determined by χ2 and Fisher`s exact test. RESULTS: HPV DNA was detected in 41 (44.6%) cervical carcinoma specimens. The prevalence rate of different HPV types was 37% (34) for HPV 16/18, 6.5% (6) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate was significantly higher in patients with HPV DNA negative cervical carcinomas (P=0.02). Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 4.9% (2 cases), compared to 21.6% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, number of positive lymph nodes, histologic subtype, maximum depth of cervical stromal invasion, maximal tumor diameter, longitudinal endocervical involvement, proportionate longitudinal endocervical involvement, tumor-cervix area quotient, maximal and minimal sagittal tumor area, parametrial involvement, vaginal involvement, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, surgical margins involvement, age) were also correlated with the presence of HPV DNA. No statistically significant association was found between the presence of HPV DNA and 17 other clinical and histopathologic variables. On the other hand recurrence rates were significantly related to tumor extent (P=0.0001), presence of regional lymph nodal metastases (P=0.0002), maximal tumor diameter (P=0.14), proportionate longitudinal endocervical involvement (P=0.007), maximal sagittal tumor area (P=0.038), parametrial involvement (P=0.0001), vaginal involvement (P=0.03), and lymph-vascular space invasion (P=0.0023). CONCLUSIONS: The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be related to recurrence rate and unrelated to various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.
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Postoperative TNM classification of breast cancer. Implications for further treatment (1989-1995)
(University of Niš Faculty of Medicine and the Department of the Serbian Medical Society Niš, 1996-06)
Yashar, Genghis
;
This study includes 1403 postoperative breast cancer specimens elaborated in our laboratory over the period of last 7 years. The average age of the patients is 54.36 years (range 22-90) and the majority are in the age groups of 41-50 and 51-60 (55.95%). The size of the primary tumour (longest diameter) belongs mostly to the category of T2 (primary tumor 2-5 cm). There are 831 cases in this group or 59.23%. Metastatic spread in the regional lymph nodes is absent in 541 cases (38.56%) and in 278 cases (19.81 %) metastatic deposits are encountered in N1biv category (bigger than 2 cm, in the greatest diameter). The most common type of breast cancer is ductal carcinoma which is present in 649 cases (46.26%). Grade of histologic differentiation is mostly moderate (G2) with 864 cases (61.58%). The majority of the patients are in the stage II of the disease (IIA +IIB = 953 cases or 67.97%). In comparision to the similar studies found in the available references it is obvious we have fewer patients in the stage I but the same number in stage II where the disease is more advanced. This means that examination and diagnosis of the breast cancer is for a step later than the degree when usually more agressive therapy is needed considering the percent of the patients in the higher stages of the disease.
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Postoperative TNM classification of cervical cancer (1989-1995)
(University of Niš Faculty of Medicine and the Department of the Serbian Medical Society Niš, 1996-06)
The aim of this study is to present and analyze the results of the application of postoperative TNM classification of cervical cancer. For this purpose we have reviewed the clinical and histopathological data of 464 patients with cervical intraepithelial (74) and invasive cancer (390) who underwent abdominal hysterectomy or radical hysterectomy with regional lymphadenectomy from March 1989 to December 1995. There were 74 (16.0%) cases of Stage 0, 211 (45.5%) of Stage I, 88 (18.9%) of Stage II, 84 (18.1%) of Stage III and 7 (1.5) cases of Stage IV. In our case series (399) we have found significant rate of discordance between clinical FIGO and postoperative stadium. The incidence of error increases progressively as the stage grows more advanced, with prevalent understaging. Cross relationships of tumor extent, incidence of lymph node metastasis, grade of tumor differentiation, histological type, and age of the patients were also studied and are discussed. These data indicate that postoperative TNM classification staging system should be applied regularly, systematically and universally.
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Prognostic significance of the human papillomavirus DNA presence in early stage cervical carcinoma
(1996-05)
;
Stavrik, George
Although the role of human papillomavirus in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. The objective of our study was to assess the prognostic significance of the presence of HPV DNA in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy. In this report the preliminary results of this larger study are presented by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 44 patients with cervical carcinoma. Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51. Clinical and histopathologic data of these patients was analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 24 (54.6%) patients, while local extension to vagina and parametrial tissues was found in 6 (13.6%) and 14 (31.8%) patients, respectively. Pelvic lymph node involvement was found in 15 (34%) patients. During the follow up period (range, 2-72, mean, 39 months), recurrences were observed in 6 patients. HPV DNA was detected in 20 (45%) cervical carcinoma specimens. The prevalence rate of different HPV types was 34% (18) for HPV 16/18, 9% (4) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate in relation to the presence of HPV DNA exhibited a trend but was not statistically significant. Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 5% (1 case), compared to 21% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, histologic subtype, maximum depth of cervical stromal invasion, longitudinal tumor diameter, tumor-cervix area quotient, parametrial involvement, vaginal invasion, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, age) were also correlated with the presence of HPV. None of these factors was found to have statistically significant relationship to the presence of HPV DNA. The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be unrelated to recurrence rate and various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.
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Computer system for data processing in a histopathology and cytopathology laboratory
(Science Printers and Publishers, 1990-06)
Stavrik, George
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Zografski, George
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Ivkovski, Ljube
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Trpkov, Kiril
A computer system for data processing in a histopathology and cytopathology laboratory handling about 16,000 new specimens a year is described. The system is used for storing all data, producing the reports, identifying unfinished cases, retrieving previous reports for patients with new specimens, tabulating specific findings, making monthly reports of diagnoses of malignancy, correlating histologic and cytologic diagnoses, surveying findings according to organ and morphology, and billing. The introduction of the computer system has provided significant augmentation of productivity and a basis for quality control, scientific research and cytopathologic correlations.
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Malignant diffuse peritoneal leiomyomatosis: A case report
(Expansion Scientifique Publications, 1998-10)
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Ivkovski, Ljube
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Yashar, Genghis
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Veljanovska, Slavica
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Vuzevski, Vojislav
Diffuse peritoneal leiomyomatosis (DPL) is a rare condition characterized by the presence of multiple abdominal smooth muscle nodules. Malignant transformation appears to be extremely rare. This report presents the eighth case with proven malignancy. The patient is a 43 year old, Caucasian, non-pregnant female, with no history of hormonal therapy, presented with a few months old history of intermittent and increasing right lower abdominal pain. In October 1996, explorative laparatomy was performed. Innumerable subperitoneal gray-white masses with firm to rubbery consistency, varying in size from 0.2 to 11.5 cm, were found scattered over the parietal peritoneum, omentum and mesentery. Several of these nodules were removed. Their microscopic appearance was variable. Most of the lesions appeared to consist of subperitonel nodules of benign-appearing smooth muscle cells. Nevertheless, some of them showed malignant characteristics, marked cellularity, and numerous mitoses. Immunohistochemical and ultrastuctural studies proved the smooth muscle origin of the tumors. During the next few months the abdominal tumors increased in size and the patient's condition progressively deteriorated. A second laparotomy was performed in March 1997. More than 40 nodules were removed together with a small bowel segment where inflammatory fistula was found. After receiving three courses of chemotherapy, the patient refused further treatment. In December 1997, the patient was admitted to the hospital with acute abdominal pain due to ileus, and the third laparotomy was performed. This additional case indicates that DPL has a low, but definite malignant potential, and suggests that meticulous examination of histologic material and careful follow up are required.
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Preoperative determination of DNA ploidy and hormone receptor status (ER and PgR) on cytologic material from breast cancer patients using image cytometry
(Karger, 1997-09)
Ivkovski, Ljube
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Zografski, George
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Yashar, Genghis
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Stavrik, George
OBJECTIVE: FNAB of breast masses is a commonly performed diagnostic test. DNA ploidy, along with estrogen (ER) and progesterone (PgR) receptors, is becoming increasingly useful as a prognostic adjunct to conventional staging and histologic grading. These prognostic parameters could be assessed preoperatively by using FNAB material. STUDY DESIGN: Sixty-three breast cancer aspirates were assayed for DNA distribution patterns and hormone receptor status with the CAS 200 Image Analyzing System. Consequently, their relations with well-established conventional prognostic factors in breast carcinoma (tumor size, lymph node status and histological grade) were analyzed. RESULTS:The majority of the primary invasive breast carcinomas were aneuploid (43/63). Most of the aneuploid tumors had histogram type IV (31/43). The data showed that breast carcinomas in which the DNA amounts of the tumor cells were euploid (histograms of types I and I1) were characterized by high levels of ER and PgR, while aneuploid types (histograms of types III and IV) had low levels of ER and PgR. Of the aneuploid breast carcinomas, 86.1% (37/43) had lymph node involvement, while only 40% (8/20) of the euploid carcinomas had lymph node involvement. The majority of the aneuploid carcinomas were of ductal type (29/43), while most of the lobular carcinomas were euploid (9/20). CONCLUSION: Our results strongly indicate a correlation between nuclear DNA distribution patterns, hormone receptor levels and postsurgical factors of prognosis in primary breast carcinomas. By determining the DNA ploidy and hormone receptor status preoperatively, the planning of treatment options available to breast cancer patients could be improved.
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Immunohistochemical study of phyllodes tumor of the breast
(Springer, 1999-09)
Yashar, Genghis
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Kubelka, Katerina
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Zografski, George
Phyllodes tumor ('PT) is a rare, fibroepithelial breast neoplasm with unpredictable prognostic and controversial therapeutic aspects. Aims: The aim of this retrospective study is to evaluate Ki-67 and CD34 antigen expression, as well as estrogen (ER) and progesterone receptor (PgR) status in stromal cells, as additional diagnostic criteria in assessing different types of PT. Methods: Routinely processed, formalin-fixed and paraffin-embedded surgical specimens from 47 cases of PT were stained by immunoperoxidase technique using Ki-67, CD34, ER and PgR monoclonal antibodies. On the basis of histopathological criteria proposed by Azzopardi, 6 malignant, 12 borderline and 29 benign PT have been evaluated. The mean size of the tumour was 9.4 cm (range 2.8-20 era). During the follow-up period (mean 50, range 2-127 months), recurrences were observed in 8 patients (17%). Results: The proliferating index determined by Ki-67 antigen expression was significantly different between histologically benign PT (19%), borderline PT (25%) and malignant PT (50%). There was a difference of the human progenitor cell CD34 antigen expression in malignant PT (50%), borderline PT (50%) and benign PT (30%). As expected, the stromal cells in various types of PT were mostly ER negative and PgR positive. Conclusions: Our preliminary results suggest that CD34 positivity and high proliferative index of Ki-67 antigen in stromal cells are more frequently associated with high grade PT. Therefore, the immunohistochemical features could provide better discrimination between different PT types. The prognostic implications of these observations should be evaluated in additional studies.

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