Faculty of Medicine

Permanent URI for this communityhttps://repository.ukim.mk/handle/20.500.12188/14

Browse

Search Results

Now showing 1 - 9 of 9

Some of the metrics are blocked by your
consent settings
HER2/neu expression in correlation with p53 and Ki-67 immunoreactivity and clinicopathological parameters in breast cancer patients.
(Blackwell Publishing, 2002-10)
Yashar, Genghis
;
;
Ivkovski, Ljube
;
Kraleva, Slavica
;
Prodanova, Irina
Introduction: Although the role of HER2/neu status is still unsettled, its determination is valuable in selecting breast carcinoma patients for adequate Herceptin therapy. Aims: The purpose of this study was to evaluate the association among HER2/neu, p53 and Ki-67 immunoreactivity, as well as clinicopathological parameters (tumour size, histopathologic grade, nuclear grade, tumour type. lymph-node status and age) in breast cancer patients. Materials and methods: HER2/neu, p53 and Ki-67 expression was determined in 169 post-operative stage I-III (UICC. 1997) breast cancer patients using the standardized DAKO HercepsTest and by immunoperoxidase technique. respectively. The results were evaluated by performing the standardized scoring system. Discussion and conclusion: HER2/neu expression was positive in 66 patients (37%). There was no association between HER2/neu expression and p53 or Ki-67 immunoreactivity as well as any clinicopathological parameter, while the values of Ki-67 and p53 were strongly interrelated (P < 0.001). Ki-67 was also in significant correlation to tumour size, lymph-node involvement and tumour type (P<0.001), while p53 was only related to patients' age (P <0.01). These results indicate that HER2/neu is an independent prognostic marker in differentiating a subgroup of high-risk breast cancer patients. Additional studies are required to adjust HER2/neu testing results to clinical outcome.
Some of the metrics are blocked by your
consent settings
Ki-67 expression in the invasion front as an additional independent significant prognostic factor influencing reccurence in early stage cervical carcinomas.
(Springer, 2005-08)
;
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
Yashar, Genghis
INTRODUCTION: The attempts to determine the prognostic significance of biological markers and their relation to human papillomavirus (HPV) infection in cervical cancer have yielded controversial results. AIMS: The aims of this retrospective study were to correlate alterations of cell proliferation, growth, differentiation and apoptosis regulatory proteins in early stage cervical carcinomas with HPV infection, histopathological and clinical parameters, and to estimate their prognostic significance. METHODS: Expression of Ki-67, p53, mdm-2, bcl-2, c-erbB-2, EGFR protein, as well as estrogen and progesterone receptors was evaluated by immunohistochemistry in operative specimens of 83 patients with early stage cervical carcinoma. The results were assessed semiquantitatively in the surface area, center and invasion front of each tumor as a percentage of the immunostained cells and/or intensity of immunostaining for each protein. The presence of HPV was assessed by conventional in situ hybridization (ISH) technique and catalyzed reporter deposition signal amplification ISH using mixed biotinylated probes to identify types 6/11, 16/18 and 31/33 or 31/33/51. RESULTS: In our case series 73 patients had a tumor limited to the uterine cervix less than 4 cm in diameter (pT1b1), while 10 patients had larger neoplasms belonging to pT1b2 category. Pelvic lymph node involvement was found in 20 patients. During the follow-up period (range, 65 -181, mean, 121 months) recurrences were observed in 9 patients. The 5, 10 and 15-year disease-free survival rate was 92.7%, 90.8% and 86.6%, respectively. Among the 18 variables pelvic lymph node involvement (P=0.0008), tumor diameter (P=0.035), depth of stromal invasion (P=0.029), histotype (P=0.0009), grade (P=0.056), HPV DNA presence (P=0.056), HPV type (P=0.043), as well as bcl-2 (P=0.035), mdm-2 (P=0.051), EGFR (P<0.0001), and Ki-67 (P=0.031) expression in the tumor’s invasion front were identified as important predictive indicators of recurrence in the univariate analysis. Independent significant prognostic factors for disease-free survival in multivariate analysis were the histotype, HPV DNA presence and Ki-67 expression. CONCLUSIONS: The invasive front of carcinomas proved to be the most important area for tumor prognosis. In addition to the detection of HPV presence and morphological parameters, Ki-67 evaluation could be used in selecting appropriate therapeutical approaches in patients with early stage cervical cancer.
Some of the metrics are blocked by your
consent settings
Potential prognostic significance of apoptosis related oncogenes: p53, bcl-2 and mdm-2 in early stage cervical carcinoma
(2003-09)
Prodanova, Irina
;
Yashar, Genghis
;
Kubelka-Sabit, Katerina
;
Zografski, George
;
Introduction: Evaluations of expression of apoptosis related oncogenes are being increasingly called upon in an attempt to better understand the carcinogenesis of cervical carcinoma and to provide possible prognostic information. The aim of this study was to analyze the expression of bcl-2, p53 and mdm-2 oncoproteins and cellular proliferative marker Ki-67 in early stage cervical carcinoma, with an emphasis on their association with human papillomavirus (HPV) infection, recurrence rate and lymph node status. Material and methods: Using immunohistochemistry, 69 radical hysterectomy specimens with cervical carcinoma (pT1b1/pT1b2) were studied. Evaluation of expression of p53, bcl-2, mdm-2 and Ki-67 was performed in surface area, center and invasion front of the neoplasms. The HPV presence was determined by CARD in situ hybridization. Results and conclusion: In the invasion front bcl-2 was expressed in 31 (45%), p53 in 37 (53%) and mdm-2 in 33 (47%) cases. HPV infection was detected in 40 (58%) cases. Carcinomas with a higher Ki-67 labeling index were more frequently HPV positive than HPV negative (82.5% vs 17.5%, p<0.01). No association was found between p53, mdm-2 or Ki-67 and either lymph node status or recurrence rate. Negative staining for bcl-2 was associated only with the presence of lymph node metastasis (74% vs 26%, p=0.05), and not with the recurrence rate. Significant correlation among expression of bcl-2, p53, mdm-2 oncoprotein and Ki-67 values was also observed. These results suggest that further study of a larger series is needed to confirm whether bcl-2, either alone or in combined evaluation with other markers, could be a useful marker to identify more aggressive behavior in early stage cervical carcinoma.
Some of the metrics are blocked by your
consent settings
Determination of estrogen, progesterone receptor and ki-67 immunoreactivity in early stage cervical carcinoma: Association with human papillomavirus infection and prognosis.
(Springer, 2003-09)
Yashar, Genghis
;
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
Zografski, George
;
Introduction: The predictive values of estrogen (ER) and progesterone receptor (PgR) status and cell proliferation kinetics in cervical carcinomas are still unsettled. The purpose of this study was to clarify the associations among ER/PgR status and Ki-67 expression and to determine their relationship to human papillomavirus (HPV) infection, recurrence rate and other clinicopathologic parameters (age, tumor diameter, depth of invasion, histotype, grade, vascular involvement, inflammatory infiltrate, lymph node status) in early stage cervical carcinomas. Materials and methods: ER, PgR and Ki-67 immunostaining was performed in 72 cervical carcinoma radical hysterectomy specimens (pT1b1/pT1b2). ER/PgR staining was scored in a semiquantitative fashion, while to evaluate the cell proliferation, the Ki-67 labelling index (LI) was assessed in the surface area, center and invasion front of each tumor. HPV status was determined by CARD in situ hybridization. Results and conclusion: ER positivity was detected in 11 (15%), while PgR positivity in 14 (20%) carcinomas. ER/PgR values were in correlation with Ki-67 LI in all three tumors' compartments (p<0.01). In contrast to ER/PgR status, Ki-67 LI was strongly associated with HPV infection (p<0.01). No relationship was found between PgR or Ki-67 immunoreactivity and either recurrence rate or any other clinicopathological variable investigated. Nevertheless, reduced ER expression was significantly associated with larger tumor diameter (p=0.04) and poor differentiation (p=0.03), as well as lymphovascular involvement (p=0.04) and lymph node metastases (p=0.02). These results suggest that ER, PgR and Ki-67 expression are closely related to neoplastic cell proliferation, probably induced by HPV infection. Their determination may provide additional prognostic information in early stage cervical carcinomas.
Some of the metrics are blocked by your
consent settings
Immunohistochemical expression and prognostic significance of DCC (deleted in colon cancer), p53 protein and proliferative marker Ki-67 in colorectal colon cancer.
(Springer, 2005-05)
Yashar, Genghis
;
;
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
Objectives: The objective of this study was to evaluate the immunohistochemical expression of Deleted in colon cancer (DCC), p53 protein and proliferating index Ki-67 in correlation with various clinico-pathological (age, sex, tumor status, lymph node involvement, localization, tumor diameter, grade of differentiation, histological type) and biomolecular parameters (loss of heterozygosity of the long arm of chromosome 18 and microsatellite instability) in colorectal cancer patients. In addition, the prognostic significance of their influence on overall survival (OS) was also estimated. Methods: A retrospective analysis of 100 patients with colorectal cancer who underwent large bowel resection with regional lymphadenectomy was conducted in the period between 1995 and 2000. All the patients were in stage II and stage III of the disease according to the postoperative TNM classification of UICC (1997) guidelines. The immunohistochemical expression of protein products of the DCC, p53 tumor suppressor genes and Ki-67 proliferating index were semi-quantitatively evaluated. Biomolecular analyses for the loss of heterozygosity of the chromosome 18q and microsatellite instability were performed with the Polymerase chain reaction (PCR) technique. Results: In our case series, 57 (57%) patients were in stage II, and the remaining 43 (43%) patients in stage III of the disease. During the follow-up period (mean 53, range 5-97 months), 41(41%) patients died of the disease. The expected 5-year OS rate was 58.6%. In the univariate analysis, tumor status, lymph node involvement, sex, age, tumor grade, p53 protein expression and Ki-67 proliferating index were parameters with prognostic significance related to OS (p<0.05). Among these variables, in the multivariate analysis the tumor status and Ki-67 proliferating index were selected as independent and significant prognostic factors related to OS (p=0.0019). According to the value of the prognostic index (PI) defined by Cox regression model, the patients were categorized in two distinct risk groups. The 5-year OS rate of the low- and high-risk group patients was 65.0% vs. 29.4% (p=0.001). The 5-year OS for stage II was 71.1% vs. 40.0% (p=0.05) and for stage III of the disease it was 54.8% vs. 25.0% (p=0.03), respectively. Conclusions: These data indicate that defining prognostic groups in each stage of the disease allow an exact and objective selection of colorectal cancer patients with different death risk. Therefore, the prognostic index (PI) as an indicator of the patient’s place in the prognostic spectrum could be a sound basis for an appropriate planning.
Some of the metrics are blocked by your
consent settings
Ovarian cellular fibromas: A cliniopathological and immunohistochemical analysis of 10 cases.
(Springer, 2007-08)
;
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
Zografski, George
BACKGROUND: Traditionally, cellular fibroblastic tumors of the ovary were classified as either cellular fibroma (CF) or fibrosarcoma. A recent study suggests that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favourable prognosis and should be diagnosed as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. In addition to clinicopathological features, immunohistochemistry may aid in further differentiating between CF and MACF, but its role has not been analyzed so far. METHOD: We retrospectively analyzed the clinicopathological and immunohistochemical features of 10 cases of ovarian cellular fibroblastic tumors diagnosed either as CF or fibrosarcoma in the last seven years. Patient records and archival pathology specimens were reviewed and immunohistochemistry was performed using pan-cytokeratin, EMA, vimentin, inhibin-alpha, calretinin, CD10, CD99, alpha-smooth muscle actin (SMA), desmin, S-100, c-kit, estrogen (ER), progesterone receptor (PR), p53, bcl-2, and MIB-1 antibody. RESULTS: Utilizing criteria proposed by Irving et al. the tumors were reclassified as CF (0-3 MFs/10 HPFs, n=5) and MACF (>4 MFs/10 HPFs, n=5). The mean age of patients with CF and MACF was 44 and 36 years, respectively. All tumors were unilateral, and the mean tumor size of CFs was 6.0 cm and 13.3 cm for MACFs. The majority of the tumors were solid; four of them had a cystic component, while ovarian surface rupture was present in one CF and one MACF. All tumors consisted of cellular, intersecting bundles of spindle cells showing slight or moderate pleomorphism. The mean highest mitotic count was 2.3 MFs/10 HPFs for CF, and 7.6 MFs/10 HPFs for MACFs. Follow-up of 4 to 79 months (mean 38 months) was available in 9 patients and was uneventful in all cases. One patient with MACF died 15 days following the operation as a result of the intercurrent disease. Immunohistochemical analyses showed that spindle cells in majority of the tumors were immunoreactive for vimentin, alpha-SMA, inhibin-alpha, calretinin, PR, and bcl-2. All tumors were negative for pan-cytokeratin, EMA, CD10, CD99, c-kit, ER, and p53, while one CF was positive for S-100, and one MACF showed positivity for desmin. In addition, the MIB-1 labeling index (LI) in MACFs was higher (mean 14.4%, range 10-25%), than that in CF (mean 5.6%, range 3-10%). CONCLUSION: Our results confirm the immunophenotypic similarity between ovarian fibromas and cellular fibromatous neoplasms, and suggest that the use of MIB-1 LI may help in differentiating between CF and MAFC.
Some of the metrics are blocked by your
consent settings
Evaluation of combined bcl-2/mdm-2 immunohistochemical expression as a prognostic factor in early stages of invasive cervical carcinomas
(Springer, 2007-08)
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
BACKGROUND: The present study was designed to evaluate the immunohistochemical expression of apoptosis regulating proteins (bcl-2, mdm-2 and p53) in correlation with proliferation (Ki-67), human papillomavirus (HPV) infection and other histopathological and clinical parameters in early stage cervical carcinomas and the estimation of their prognostic significance. Special attention was given to combined bcl-2/mdm-2 immunophenotypes in predicting the recurrence of the disease. METHOD: The subject of this study was a series of 83 surgically treated patients with cervical carcinoma confined to the uterine cervix (pT1b1/1b2), who subsequently received complete radiotherapy. The presence of HPV DNA was determined by the conventional method of in situ hybridization (ISH) and catalyzed reporter deposition signal amplification ISH. The immunostaining was performed using avidin-biotin-peroxidase complex method and the expression of the biological markers was semiquantitatively evaluated as the percentage of immunostained cells. RESULTS: During the clinical follow-up (mean 120.7, range 4.4-181 months) a relapse was diagnosed in 9 (10.8%) patients and the expected 5-, 10- and 15- year disease-free survival was 92.7%, 90.8% and 86.6%, respectively. The results of the univariate analysis indicate that significant predictive indicators for recurrence are: lymphonodal status, maximal tumor diameter, depth of stromal invasion, histological type and HPV DNA presence and type. Immunohistochemical markers showed the following correlations: increased expression of Ki-67 (P=0.031) and bcl-2 negativity (P=0.047) correlated with poor disease-free survival, while mdm-2 positivity showed borderline significance (P=0.051) and p53 expression had no influence on disease-free survival. Additional evaluation of combined bcl-2/mdm-2 expression showed that cases with bcl-2+/mdm-2- and bcl-2-/mdm-2+ immunophenotype had better survival (P=0.048) compared to bcl-2+/mdm-2+ and bcl-2-/mdm-2- phenotype. In the multivariate analysis, histological type, HPV DNA presence and the expression of Ki-67 have been selected as the most significant independent prognostic parameters (P=0.0024). CONCLUSION: The evaluation of combined bcl-2/mdm-2 immunohistochemical expression provides more relevant information for the prediction of the recurrence of the disease than their individual expression. However, neither individual expression of bcl-2 and mdm-2 nor their combined immunohistochemical expressions are independent predictors of prognosis in early stages of invasive cervical carcinomas.
Some of the metrics are blocked by your
consent settings
Prognostic value of cell proliferation, growth and differentiation regulatory proteins in early stage cervical carcinoma
(Springer, 2006-05)
;
Yashar, Genghis
;
Kubelka-Sabit, Katerina
;
Prodanova, Irina
Objectives: The aim of this study was to evaluate the immunohistochemical expression of cell proliferation, growth, and differentiation regulatory proteins in early stage cervical carcinoma and to assess their prognostic value by exploring their relationships to various clinicopathological characteristics (age, lymph node involvement, tumor diameter, depth of invasion, thickness of uninvolved cervical stroma, histotype, grade, lymphvascular space invasion, inflammatory infiltrate), human papillomavirus (HPV) status and influence on disease-free survival. Methods: This retrospective study comprised 83 patients, all subjected to radical hysterectomy with bilateral pelvic lymphadenectomy for early stage cervical carcinoma and postoperative irradiation therapy. Expression of Ki-67, c-erbB-2, EGFR protein, as well as estrogen and progesterone receptors was evaluated by immunohistochemistry using avidinbiotin-peroxidase complex method. The results were assessed semiquantitatively in the surface area, center and invasive front of each tumor as the percentage of the immunostained cells and/or intensity of immunostaining for each protein. The presence of HPV was assessed by conventional in situ hybridization (ISH) technique and catalyzed reporter deposition signal amplification ISH using mixed biotinylated probes to identify types 6/11, 16/18 and 31/33 or 31/33/51. RESULTS: In our case series, 73 (88%) patients had a tumor limited to the uterine cervix less than 4 cm in diameter (pT1b1), while 10 (12%) patients had larger neoplasms belonging to pT1b2 category. Pelvic lymph node involvement was found in 20 (24%) patients. During the follow-up period (range, 65-181, mean, 121 months) recurrences were observed in 9 patients. The 5-, 10- and 15-year disease-free survival rate was 92.7%, 90.8% and 86.6%, respectively. Important predictive indicators of recurrence in the univariate analysis were pelvic lymph node involvement (P=0.0008), tumor diameter (P=0.035), depth of stromal invasion (P=0.029), histological type (P=0.0009), grade of differentiation (P=0.056), HPV DNA presence (P=0.056), HPV type (P=0.043), as well as Ki-67 (P=0.031), and EGFR protein (P=0.0066) expression in the tumor’s invasive front. Among these variables, however, the histological type, HPV DNA presence, Ki-67 and EGFR protein expression were identified as independent significant prognostic factors for disease-free survival in multivariate analysis using Cox regression model. Conclusions: The invasive front of carcinomas proved to be the most important area for the evaluation of prognostic significance of the expression of cell proliferation, growth, and differentiation regulatory proteins. In addition to the detection of HPV presence and morphological parameters, the evaluation of Ki-67 and EGFR protein expression may provide additional prognostic information in patients with early stage cervical carcinomas.
Some of the metrics are blocked by your
consent settings
Immunohistochemical expression and prognostic significance of the biological markers bcl-2, p53, mdm-2 and ki-67 in early stages of invasive cervical carcinomas
(Springer, 2006-05)
Prodanova, Irina
;
Kubelka-Sabit, Katerina
;
Yashar, Genghis
;
Objectives: The objectives of this study were the evaluation of the immunohistochemical expression of apoptosis regulating proteins (bcl-2, mdm-2 and p53 protein) in correlation with proliferation (Ki-67), human papillomavirus (HPV) infection and other histopathological and clinical parameters in early stage cervical carcinomas and estimation of their prognostic significance. Methods: The subject of this study was a series of 83 surgically treated patients with cervical carcinoma confined to the uterine cervix, who subsequently received complete radiotherapy. The presence of HPV DNA in the neoplasm was determined by the conventional method of in situ hybridization (ISH) and catalyzed reporter deposition signal amplification ISH using mixed biotinylated probes to identify types 6/11, 16/18 and 31/33 or 31/33/51. The immunohistochemical expression of the biological markers was semiquantitatively evaluated as the percentage of immunostained cells in the three compartments of the neoplasm: the surface, the middle layer and the invasive front. Results: 73 patients had a tumor confined to the uterine cervix less than 4 cm in diameter (pT1b1) and the other 10 had larger neoplasms that belong to the pT1b2 category. Regional lymph node involvement was found in 20 (24%) of the patients. During the clinical follow-up (mean, 120.7, range 4.4-181 months) a relapse was diagnosed in 9 (10.8%) patients, 6 of which (7.2%) died of the disease. The expected 5-, 10- and 15- year overall survival was 94.4%, 92.7% and 92.7%, and disease-free survival was 92.7%, 90.8% and 86.6%, respectively. The results of the univariate analysis indicate that significant predictive indicators for recurrence are: lymphonodal status, maximal tumor diameter, depth of stromal invasion, histological type, HPV DNA presence and type, and the immunohistochemical expression of bcl-2, mdm-2 and Ki-67 in the invasive front of the neoplasm. In the multivariate analysis, histological type, HPV DNA presence and the expression of Ki-67 in the invasive front have been selected as the most significant independent prognostic parameters (P=0.0024). The value of the prognostic index (PI), calculated using the Cox regression model, provided the basis on which the patients were classified into two distinct risk groups with significantly different disease-free survival period (P=0.0009). Conclusions: The results indicate that the invasive front of the neoplasms proved to be the most important area for the evaluation of immunohistochemical expression of biological markers. The prognostic index as an indicator of the patient’s place in the prognostic spectrum enables the identification of the risk group of patients in whom, due to a higher risk of relapse, better results are to be expected with the application of more aggressive therapy.

Faculty of Medicine

Browse

Filters

Settings

Sort By

Results per page

Search Results