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J Kupryjańczyk

Publications and source records attributed to J Kupryjańczyk.

At least 19 recordsLinked to original sources
PubMed2006

PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations.

OBJECTIVE: We aimed to evaluate frequency of PTEN mutation, LOH and expression in ovarian tumors. In search for a molecular pathway, we confronted PTEN gene mutations with TP53, K-RAS and BRCA1 gene status in the same tumors. We also evaluated clinical significance of PTEN expression in a subgroup of patients uniformly treated with platinum-based regimens. METHODS: Molecular analysis was performed on 105 ovarian tumors (100 carcinomas) with the use of the SSCP and sequencing. Seventy-six tumors were analyzed for LOH at 10q23 locus with the use of six polymorphic markers. Immunohistochemical PTEN expression was done on paraffin-embedded material. Multivariate and univariate analysis was performed with the STATA program. RESULTS: PTEN mutations occurred in 5/100 (5%) of all carcinomas and in 3/15 (20%) of endometrioid carcinomas (EC). Low-grade EC that developed in borderline tumors had PTEN and/or K-RAS mutation (4/5, 80%), while high-grade EC had TP53 mutations only. There was a reverse association between PTEN and TP53 mutations (P = 0.005). LOH at PTEN locus was found in 60% of endometrioid and in 28% of serous and clear cell carcinomas. PTEN expression did not associate with PTEN mutations or LOH. Strong PTEN expression diminished risk of death in a TP53 positive group only (HR = 0.35, P = 0.029). CONCLUSION: Our results suggest that PTEN mutations may play a role in a development of low-grade endometrioid tumors. PTEN haploinsufficiency caused by LOH or epigenetic events may possibly contribute to development of other histological types and may be an adverse prognostic factor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Geographical variations in TP53 mutational spectrum in ovarian carcinomas.

The TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38%vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11%vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9%vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273(HIS) codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273(CYS) codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.

Adenocarcinoma, Clear Cell↗
PubMed2004

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

Adult↗
PubMed2003

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Adult↗
PubMed2003

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Adult↗
PubMed2002

Nijmegen breakage syndrome gene (NBS1) alterations and its protein (nibrin) expression in human ovarian tumours.

We looked for NBS1 gene (602667) alterations and changes in nibrin expression in 162 human gynaecological tumours, mostly ovarian. Exons 6-8 and 10 of the NBS1 gene were evaluated by the SSCP and direct sequencing method. Nibrin expression was detected immunohistochemically with the use of the p95NBS1 (Ab-1) antibody. The 657del5 mutation (Slavic mutation) was found in two of 117 carcinomas studied (1.7%) - in both cases it was present in the germline; one of these tumours showed loss of heterozygosity (LOH) for the 657del5 mutation and loss of nibrin expression. We have found three types of novel germline intron variants: (1) two concomitant transitions (G to A) at bases 14009 and 14256; (2) C to T transition at base 13998; (3) G to C transversion at base 20035. Among the carcinomas studied, the intron variants were associated with a clear cell histological type (p = 0.004). Our results may suggest that NBS1 gene alterations contribute to the development of rare ovarian carcinomas. LOH for 657del5 in tumour tissue may support the hypothesis that the NBS1 gene functions as a tumour suppressor.

Abnormalities, Multiple↗
PubMed2000

Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction.

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and were sequenced directly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochemically. A weighed multiple logistic regression model was applied. Apoptotic index (AI) ranged 0.02-0.18 (mean 0.11); proliferation index (PI) ranged 3-90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumulation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The AI was positively associated with the presence of p53 gene mutation (P = 0.011). However, the PI included into the analysis did positively influence the AI (P = 0.02) and diminished the association with p53 gene mutation (P = 0.082). The AI was negatively associated with good histological differentiation (P = 0.0006), the serous tumour type (P = 0.002), and diffuse bcl-2 expression (P = 0.025). Strong bcl-2 expression was associated with endometrioid tumour type (P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results suggest that histological tumour type and grade are major determinants of spontaneous apoptosis in ovarian carcinomas; p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fraction. This, in turn, suggests p53-independency of spontaneous apoptosis in ovarian carcinomas.

Adolescent↗
PubMed1998

Desmin expression in reactive mesothelium: a potential aid in evaluation of gynecologic specimens.

Desmin is a marker of smooth and striated muscle, but evidence is accumulating that it may be expressed by human mesothelium. The aim of this study was to describe desmin expression in normal, reactive, and hyperplastic peritoneal mesothelium, and to evaluate its potential use as a marker for differentiating between epithelial and mesothelial proliferations. We immunohistochemically studied 27 tissue specimens (from 22 patients) with reactive mesothelium, including omentum (n = 14), fallopian tubes (n = 7), ovaries (n = 3), ascitic fluid (n = 1), and peritoneal washings (n = 2). Ovarian surface epithelium (OSE) from 9 cases and 28 ovarian surface epithelial tumors was evaluated for comparison. The desmin expression pattern in the mesothelium, which was similar to but less consistent than that of cytokeratins, was evident in flat and reactive mesothelium, including hyperplastic mesothelial sheets and mesothelium entrapped in clefts. Mesothelial pseudoglandular structures, present in three cases, were predominantly negative for desmin. Desmin expression was observed in the OSE in 4 of 9 cases but not in any mullerian-derived epithelium or mullerian type tumor. Thus, in contrast to cytokeratins, desmin discriminated mesothelial cells from mullerian type epithelia. Compared with vimentin, desmin discriminated mesothelial cells from other tissues except muscle cells. We conclude that desmin may be used in addition to cytokeratins and vimentin as a marker of peritoneal mesothelium.

Ascitic Fluid↗
PubMed1997

Neuroendocrine tumors of the ovary--a review.

Neuroendocrine tumors are a heterogeneous group of separate clinico-pathological entities which have a common characteristic i.e. expression of endocrine differentiation potential. In the ovary, the term "neuroendocrine" relates mainly to widely known carcinoids, but it may also be applied to rare neuroendocrine carcinomas of non-small-cell type and small cell carcinomas of pulmonary type. Ovarian carcinoids develop in pure form or in association with other tumors, mainly teratomas. They originate from endocrine cells, either of teratomatous origin or possibly also indigeneous. Ovarian neuroendocrine carcinomas belong most probably to surface epithelial neoplasms, which express endocrine pathway of differentiation. The neuroendocrine carcinomas of non-small-cell type are characterized by the presence of islands, sheets, and trabeculae with little intervening stroma (organoid growth pattern) and cellular homogeneity. However, they are higher-grade than carcinoids. To date, eight ovarian neuroendocrine carcinomas have been described, and all developed in association with glandular müllerian type component. The neuroendocrine differentiation was confirmed by presence of at least two specific markers (argyrophilia and/or argentaffinity, chromogranin A). Initial observations suggest that the presence of neuroendocrine differentiation carries bad prognosis. Primary ovarian small cell carcinomas of the pulmonary type do not differ histologically from their counterparts in other organs. They are composed of small cells with scanty cytoplasm and oval to spindle-shaped nuclei. About 13 cases of this tumor type in the ovary have been reported. Some of them developed in pre-existing benign or malignant ovarian tumors. Argyrophilia and positive chromogranin A staining were seen in two cases only. The prognosis for this tumor type is poor.

Carcinoid Tumor↗
PubMed1994

p53 expression in ovarian borderline tumors and stage I carcinomas.

Seventy-nine ovarian serous and mucinous borderline tumors, 36 stage I carcinomas and 39 stage II-IV carcinomas were studied for p53 protein accumulation with monoclonal antibody PAb1801.p53 protein was expressed in 14% of borderline tumors, 36% of stage I carcinomas, and 64% of higher stage carcinomas. All immunopositive carcinomas accumulated p53 protein in the primary tumor, and 95% of them showed concordance in staining among different tissue blocks. A difference in frequency of p53 protein accumulation between stage I and higher stage serous carcinomas was not statistically significant. p53 positivity was associated with microinvasion, microcarcinoma and coexistent carcinoma in mucinous borderline tumors (P = .025). An association between p53 protein expression and poor tumor differentiation in Stage I carcinomas as statistically significant (P = .03). p53 positivity was observed in a poorly differentiated endometrioid carcinoma as well as in adjacent benign endometriotic tissue. These results suggest that p53 abnormalities may be early events in ovarian cancer, possibly contributing to malignant transformation of some borderline tumors, endometriosis and other carcinoma precursors.

Adenocarcinoma, Mucinous↗
PubMed1993

p53 gene mutations and protein accumulation in human ovarian cancer.

Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal müllerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ-line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb1801. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer.

Amino Acid Sequence↗
PubMed1991

Progesterone receptor expression in human cervix uteri.

Progesterone receptor (PR) expression was studied in human cervix uteri from 21 cases. The study was performed on fresh frozen material with application of mouse anti-rabbit PR antibody and the immunoperoxidase method. Most cervical PR-s were present in the glandular epithelium and in smooth muscle cells. The results suggest that PR expression in the cervical glands is hormone-dependent; it was strongest in the presence of estrogen-stimulated endometrium, weaker with progesterone stimulation and absent in atrophy. The ectocervical epithelium contained relatively few progesterone receptors.

Adult↗
PubMed1990

Epidermal growth factor receptor expression in the normal and inflamed cervix uteri: a comparison with estrogen receptor expression.

The expression of epidermal growth factor receptor (EGFR) was studied in the normal and inflamed cervix uteri, and the results were compared with estrogen receptor (ER) expression. The study was performed on fresh frozen specimens from 18 cases by means of immunohistochemistry, with application of EGFR1 antibody and an ER-ICA kit (Abbott, Wiesbaden, F.R.G.). The EGFR was expressed by the basal and parabasal layers of ectocervical and metaplastic epithelium and by reserve cells. No cyclic fluctuations in EGFR expression were noted. The glandular epithelium did not express EGFR. Some glands stained positive in the region of the basement membrane. Staining was not diminished in inflammatory foci, in contrast to ER expression, which was trace or absent. This was observed in both normal and dysplastic squamous epithelium. It may be assumed that the change of the normal relationship between ERs and EGFRs influences the process of proliferation and maturation of the squamous epithelium and may play a role in its disturbances.

Adolescent↗
PubMed1990

[Endometrial gestagen effect in patients with Krukenberg tumors--report of two cases].

The paper describes two cases of Krukenberg tumors with accompanying "arrested secretion" pattern in the endometrium. Both patients presented with a vaginal bleeding--in one case a suspicion of Krukenberg tumor was made solely on the basis of evaluation of curettage. In postmenopausal patients whose endometrium presents "arrested secretion" pattern, and who deny any progestagen therapy or substitution, the possibility of an ovarian metastatic tumor should be taken into account.

Adult↗
PubMed1989

Cycle- and function-related changes in lectin binding to human endometrium: a histochemical study with pronase treatment.

Forty-eight endometrial biopsy specimens were obtained during a normal menstrual cycle, during pregnancy and from patients with dysfunctional bleeding. The specimens were examined for Peanut (PNA), Soybean (SBA), Vicia villosa (VVA), Phytohem- (PHA), Lens culinaris (LCA) and Concanavalin (succ. Con A) agglutinin binding. The study was performed on paraffin sections using the pronase digestion and either the peroxidase-antiperoxidase or the avidin-biotin-peroxidase method. Cycle-related changes of the PNA, SBA, VVA, and to some degree PHA binding, were based on the transfer of the cytoplasmic reaction toward the glandular lumena. PNA + and SBA + material moved to the cell surface at the transition of the follicular and luteal phase and before the basal vacuolization appeared. Functional disturbances mainly influenced the intensity of the reaction. It was true only for those lectins, whose binding pattern showed cycle-related changes. In curettings from patients with a prolonged menstrual cycle the lectin binding seen in normal late secretory endometrium was absent or significantly diminished. Lectin binding to the endometrial surface epithelium was variable; PHA was the only lectin, the binding pattern of which followed cyclic changes in the glycocalyx, detected previously by means of PAS and alcian blue methods.

Adult↗
PubMed1989

Adenomatoid tumour of the ovary and uterus in the same patient.

The paper describes an unusual case of two adenomatoid tumours in one patient. The first tumour was diagnosed in a hysterectomy specimen, when the patient was 39 years old. A wedge-shaped fragment was intraoperatively obtained from the left ovary. An adenomatoid tumour of the left ovary was diagnosed two years later. Multiple talc granulomas, inclusion cysts, and adhesions were found in close proximity to the tumour. It seems from this observation and from the reviewed literature that talc crystals as well as repair and inflammatory processes should be taken into account as initiating factors in the development of ovarian adenomatoid tumours in patients with susceptibility to such tumours.

Adult↗
PubMed1988

Estrogen receptor distribution in the normal and pathologically changed human cervix uteri: an immunohistochemical study with use of monoclonal anti-ER antibody.

Normal and pathologically changed structures of human cervix uteri were examined for estrogen receptor (ER) content using monoclonal antiestrophilin antibody (H 222 SP gamma) and the peroxidase-antiperoxidase method (PAP). The study was performed on fresh-frozen cervical specimens from 30 women; the staining was evaluated semiquantitatively. The ER expression in cervical mucosa was generally strong and comparable to the ER expression by proliferating endometria. The only exception was the endocervical stroma, which showed distinctly weaker specific staining than other cervical structures. This might account for ER concentration gradients observed in biochemical studies. The ER content in endocervical glands varied in different cases and in different areas of the same specimen, but no correlation to the functional activity of the genital tract or to the morphology of the glands could be found. The squamous epithelium of the portio vaginalis contained relatively large amounts of ER in the basal, parabasal, and intermediate layers. The superficial layer was ER-negative. The only factor we observed that strongly influenced the ER content in cervical mucosa was a local inflammatory process. Our results suggest that the synthesis of ER in cervical epithelium can be influenced by underlying stroma.

Adult↗