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A Semczuk

Publications and source records attributed to A Semczuk.

At least 19 recordsLinked to original sources
PubMed2004

K-ras gene point mutations and p21ras immunostaining in human ovarian tumors.

It is well recognized that genetic alterations within oncogenes, tumor suppressor genes, DNA mismatch repair and excision repair genes contribute to tumorigenesis within the human ovary. This study was undertaken to screen for the existence of K-ras gene point mutations in paraffin-embedded slides randomly selected from benign and malignant ovarian tumors applying the PCR-RFLP technique. Expression of p21ras was also assessed in 30 primary ovarian adenocarcinomas immunohistochemically. K-ras codon 12 point mutations occurred in nine of 40 (22.5%) cases. They were not identified in two benign mucinous cystadenomas, but in one out of two (50%) mucinous tumors of LMP (low malignant potential), in five out of 30 (17%) ovarian adenocarcinomas, and in one case of adenocarcinoma metastatic to the ovary. K-ras activation was also detected in one out of four (25%) sex cord-stromal cell tumors (folliculoma), and in one dysgerminoma. None of these tumors exhibited K-ras codon 13 point mutations. Gene alterations were more frequently found in mucinous than in non-mucinous (30% vs 10%) tumors, although the difference did not reach significance (p > 0.05). The frequency of K-ras point mutations was correlated neither with clinical nor with pathological variables of cancer. Cytoplasmic p21ras was expressed in all adenocarcinomas negative for K-ras point mutations, whereas one of five (20%) K-ras-positive tumors exhibited lack of immunoreactivity. In conclusion, these findings confirm the role of K-ras activation in mucinous ovarian tumors. p21ras expression is not necessarily associated with K-ras gene alterations in human ovarian adenocarcinomas.

Adenocarcinoma↗
PubMed2001

K-ras exon 2 point mutations in human endometrial cancer.

In the present study, we screened for the K-ras exon 2 point mutations in a group of 87 gynecological neoplasms (82 endometrial carcinomas, four carcinomas of the uterine cervix and one uterine carcinosarcoma) using the non-isotopic PCR-SSCP-direct sequencing techniques. Direct sequencing analysis revealed CAA-->CAC (Gln-->His) K-ras codon 61 point mutations in two (2.4%) of the 82 endometrial carcinomas mentioned above. These two cases were endometrial endometrioid carcinomas at an early clinical stage of disease (stage IB and IC due to FIGO). Those endometrial carcinomas that showed K-ras exon 2 point mutations revealed a strong positivity for heterogeneous nuclear retinoblastoma protein staining; none of these, however, have had the K-ras codon 12 point mutation. In addition, there were no K-ras gene point mutations in three endometrial carcinomas lacking the Rb protein immunohistochemically. None of the cervical carcinomas tested had K-ras gene point mutations, whereas one carcinosarcoma harbored K-ras codon 61 point mutation (CAA-->CAC). In conclusion, our data support the view that K-ras exon 2 point mutations are rare events in human endometrial cancer. Rb and K-ras gene abnormalities may occur independently of each other during endometrial carcinogenesis in humans.

Aged↗
PubMed2001

Immunohistochemical analysis of MIB-1 proliferative activity in human endometrial cancer. Correlation with clinicopathological parameters, patient outcome, retinoblastoma immunoreactivity and K-ras codon 12 point mutations.

To test the prognostic utility of MIB-1 in human endometrial neoplasias, the proliferative activities of fifty-two endometrial carcinomas obtained from Polish women were assessed. We also investigated the relationship between the MIB-1 Proliferative Index and the well-known clinicopathological features of cancer (clinical stage, histological type, histological grade, depth of myometrial invasion), patient's age, overall survival, retinoblastoma immunostaining and K-ras codon 12 point mutations. The mean MIB-1 Proliferation Index was 43.8%, with a median of 36.0%. Due to the great intratumour heterogeneity of the immunoreaction, the Index ranged from 0% to 98%. A significant relationship was noted between MIB-1 expression and histological grading (p = 0.0004) and myometrial invasion of cancer (p = 0.01). Multivariate Cox regression demonstrated that the clinical stage was the only independent prognostic factor during follow-up (p = 0.025). There was a tendency towards a poorer outcome for women with a Proliferative Index of > 31% than for patients whose Index was < or = 31%; the difference, however, did not reach significance (p = 0.25; log-rank test). Interestingly, uterine cancers lacking retinoblastoma protein expression had a mean MIB-1 Proliferation Index that was nearly twice as high as in those neoplasias that stained positively for retinoblastoma (70.33% and 42.14%, respectively; p = 0.09; Mann-Whitney-U test). There were no significant differences between K-ras codon 12 point mutation-positive and -negative endometrial carcinomas regarding the proliferative activity of the cancer (mean Indexes 47.6% and 43.8%, respectively; p = 0.66, Mann-Whitney-U test). Our data support the view that MIB-1 proliferative activity was significantly increased with a decrease of the histological grading and with the myometrial invasion of human endometrial cancer.

Adult↗
PubMed2001

"Low-risk" and "high-risk" HPV-infection and K-ras gene point mutations in human cervical cancer: a study of 31 cases.

To analyze the coexistence of human papilloma virus (HPV) infection and K-ras gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and 24 invasive) cervical carcinomas for "low-risk" (types 6 and 11) and "high-risk" (types 16 and 18) HPVs and K-ras point mutations using PCR-based technology. "Low-risk" HPVs were not detected in the group investigated; however, 20 of 31 (64%) cases were HPV 16 positive, while HPV 18 was found in only three (9.7%) samples (HPV 6/11 v. HPV 16/18, p < 0.0001; HPV 16 v. HPV 18, p < 0.0001; Fisher's exact test). There was a K-ras codon 12 point mutation in two of 31 (6.4%) neoplasms, with none of the cases showing a K-ras codon 13 point mutation. Two moderately differentiated squamous carcinomas showed K-ras exon 2 gene alterations. Interestingly, none of the pre-invasive cervical carcinomas displayed K-ras gene point mutations. The mean patient age did not differ significantly in the number of HPV-positive and -negative cases. A coexistence of "high-risk" human papillomavirus DNA with K-ras gene alterations was observed in three of 31 (9.7%) neoplasms (one IIA and two IB moderately differentiated cervical carcinomas). Our results suggest that "high-risk" HPVs coexist with K-ras gene alterations in a subset of moderately differentiated carcinomas of the cervix uteri.

Adenocarcinoma↗
PubMed2001

[Assessment of the PCNA and P53 proteins expression in the proliferative, hyperplastic and neoplastic human endometrium].

In the current study, PCNA and p53 proteins were immunohistochemically studied in the proliferative (n = 5), hyperplastic (n = 4) and neoplastic (n = 20) human endometrium. PCNA immunostaining was noted in 2 out of 5 (40%) proliferative, 4 out of 4 (100%) hyperplastic, and in 18 out of 20 (90%) neoplastic slides. Concomitant PCNA and p53 expression was reported in 12 out of 20 (60%) malignant tumors. All non-endometrioid neoplasms were PCNA-positive, suggested this proliferative marker is commonly expressed in the unfavorable histological types of endometrial cancer.

Adult↗
PubMed2000

p53 protein detection by the western blotting technique in normal and neoplastic specimens of human endometrium.

The aim of the study was to investigate p53 protein expression by the Western blotting technique (estimated by integrated optical density - IOD) in normal (n = 13) and neoplastic (n = 40) human endometrial tissues as well as in a case of uterine carcinosarcoma and in a specimen of the botryoid sarcoma of the uterine cervix. p53 protein levels were correlated with patients' age as well as with conventionally used clinicopathological features of the endometrial neoplasm. A statistically significant difference was noted in p53 levels in the nuclear, but not in the cytoplasmatic, fraction between the normal endometria and endometrial cancer tissues (P < 0.0001). In the neoplastic endometria, nuclear p53 protein expression was higher than in cytoplasmatic fraction, and the difference was significant (P < 0.05). Higher nuclear p53 protein levels correlated with advanced histological grading of endometrioid endometrial carcinomas, but no relationship was noted between p53 protein expression and patients' age, clinical stage, histological type or depth of myometrial invasion. A case of uterine carcinosarcoma and a specimen of a botryoid sarcoma of the uterine cervix expressed nuclear p53 oncoprotein (57 IOD and 89 IOD, respectively). In conclusion, we found a statistically higher nuclear p53 levels in malignant as compared to normal human endometrial specimens by the Western blotting technique. Although there were no significant differences between p53 expression and clinicopathological features of the neoplasm (except poor histological grading), further studies are necessary to evaluate the influence of p53 nuclear/cytoplasmatic levels on the clinical outcome of Polish patients suffering from endometrial cancer.

Age Factors↗
PubMed2000

RB protein expression in human endometrial carcinomas--an immunohistochemical study.

The aim of the current study was to investigate the immunohistochemical expression of the retinoblastoma protein (pRB) in formalin-fixed, paraffin-embedded specimens obtained from 62 patients suffering from endometrial cancer. The avidin-biotin-peroxidase detection system with microwave pretreatment and the mouse anti-human NCL-RB1 monoclonal antibody were used. Heterogeneous nuclear immunostaining for the pRB was generally observed in the glandular cells in 59 out of 62 (95%) endometrial carcinomas, while stromal components were unreactive. In one case of stage Ic endometrioid adenocarcinoma, a small percentage of glandular cells (5%) stained positively with the anti-RB antibody, while two other tumors (stage IIa adenosquamous carcinoma and stage IIIa endometrioid adenocarcinoma) were pRB negative. In the cases with concomitant hyperplastic and neoplastic endometrial lesions, pRB immunoreaction was heterogeneous in the hyperplastic endometrial cells and in the adjacent neoplastic endometrium. Moreover, eight cases of endometrial carcinoma harboring K-ras codon 12 gene point mutation overexpressed pRB (more than 80% of glandular endometrial cells were positive) immunohistochemically, while none of three pRB negative slides had a K-ras gene alteration. Our data support the view that the pRB is expressed in most of the human endometrial neoplasms, but the lack of pRB immunoreactivity may correspond with the retinoblastoma gene rearrangements in a subset of advanced endometrial carcinomas.

Adenocarcinoma↗
PubMed2000

[Prognostic value of serum MMP-2 level in uterine cancer affected women].

OBJECTIVES: Matrix metalloproteinase-2 (MMP-2) which can degrade type IV collagen is implicated in cancer invasion and metastasis. The aim of the study was to evaluate the serum MMP-2 level in patients with endometrial carcinoma (EC) and to compare the level with histological grade G1 to G3 in relation to clinical staging I degree-IV degrees as well as myometrial invasion (M. < 1/2, M. > 1/2). MATERIALS AND METHODS: The study group consisted of 30 patients with EC. MMP-2 serum levels were measured with specific one-step sandwich enzyme immunoassay (Amersham Life Science). Statistical analysis was performed by Mann-Whitney test and p value < 0.05 was considered as statistically significant. RESULTS: The statistically elevated enzyme level was observed in patients presenting II degrees-IV degrees clinical stage of EC in comparison to women with I degree stage of this carcinoma. There were no significant correlations between MMP-2 serum levels and grades of histological differentiation as well as depth of myometrium invasion. CONCLUSIONS: MMP-2 serum level is statistically higher in clinically advanced stages of EC. This enzyme seems to be useful in monitoring of therapeutical efficacy or screening for the recurrences of the disease.

Adult↗
PubMed2000

Total sialic acid content in endometrial cancer tissue in relation to normal and hyperplastic human endometrium.

The aim of this study was to measure the total sialic acid (TSA) content in endometrial cancer tissue and to assess its relationship to clinicopathologic features of the malignancy. Tissue TSA content was measured in 42 women with endometrial cancer, 14 women with endometrial hyperplasia, and 45 women with normal endometrium in the proliferative phase (n = 16) and secretory phase (n = 29) of the menstrual cycle using the Warren procedure. The mean TSA content in endometrial cancer (2.16 micromol/gm) was significantly higher in comparison to normal endometrium in both proliferative (1.23 micromol/gm) and secretory (1.51 micromol/gm) phases. TSA content in the hyperplastic endometrium (1.56 micromol/gm) was higher as compared to the normal endometrium, but the differences were not statistically significant. An increased TSA content in the neoplastic endometrium in relation to the normal endometrium supports the view that the development of endometrial cancer is associated with the increasing content of sialic acid in the tumor tissue.

Aged↗
PubMed1999

Analysis of p53 and K-ras genes and their proteins in a sarcoma botryoides of the uterine cervix.

Several data indicate that the activation of oncogenes and growth factors as well as inactivation of the tumor suppressor genes are implicated in the development of human neoplasms, including sarcomas. In the present study we described a case of the extremely rare, but highly malignant neoplasm of the female genital tract known as sarcoma botryoides of the uterine cervix and assessed, using molecular and an immunohistochemical analysis, p53 and K-ras alterations in the tumor. A point mutation in exon 6 of the p53 tumor suppressor gene was found but no K-ras gene point mutations at codons 12, 13 and 61 were detected using molecular analysis. p53 protein was overexpressed in more than half of the neoplastic cells, however, ras p21 protein expression was not immunohistochemically detected. Our data indicate that p53, but not K-ras gene alterations may play a role in the development and progression of sarcoma botryoides of the uterine cervix.

Adolescent↗
PubMed1998

bcl-2 protein expression in endometrial carcinoma: the lack of correlation with p53.

bcl-2 expression was examined on paraffin-embedded specimens in proliferative, hyperplastic, and neoplastic human endometrium by immunohistochemistry. The results of bcl-2 immunostaining in endometrial carcinomas were compared with clinicopathological indicators as well as with p53 accumulation. The streptavidin-peroxidase detection system was used and the intensity and the distribution of immunostaining was evaluated semiquantitatively by counting H-score values. Expression of the bcl-2 protein was found in 2 out of 5 cases of proliferative endometrium (mean H-score 0.4, range 0.35-0.45), 4 out of 5 cases of simple hyperplasia (mean H-score 1.23; range 1.0-1.4), 4 out of 5 cases of complex hyperplasia (mean H-score 1.1; range 0.7-1.2) and in 7 out of 25 cases of endometrial carcinoma (mean H-score 0.48; range 0.35-0.65). All bcl-2 positive slides were obtained from patients who had endometrial cancer and who were in the early (stage I due to FIGO) clinical stage of the disease. bcl-2 expression was not related to age, surgical stage or histopathological features, and neither was there an inverse correlation between bcl-2 immunostaining and p53 expression reported in the study of neoplastic endometrium. Our data indicate that mechanisms other than p53 may play a role in the regulation of bcl-2 expression in endometrial carcinomas.

Aged↗
PubMed1998

K-ras gene point mutations in human endometrial carcinomas: correlation with clinicopathological features and patients' outcome.

In order to evaluate the role of K-ras gene point mutations in the progression of endometrial carcinoma, we applied the polymerase chain reaction/restriction-fragment-length polymorphism technique to 57 tumours surgically removed from women of Polish origin. We assessed the relationship between K-ras gene activation and clinicopathological features as well as patients' outcome. Mutational activation in codon 12 of the K-ras gene was detected in 8 out of 57 (14%) endometrial carcinomas, while in codon 13 of the K-ras gene no point mutations were noted. A correlation between the histological type of the tumour and codon 12 K-ras gene mutation was noted (P < 0.05; Fisher exact test). K-ras gene mutation was not related to the patients' age, surgical stage, histological grade or to the depth of myometrial invasion. A trend towards a poorer prognosis was noted during the follow-up of patients whose tumours had shown K-ras codon 12 point mutations, but the difference was not significant (P = 0.06; log-rank test). Our data indicate that point mutations in codon 12 of the K-ras gene are a rare event in human endometrial carcinomas. The lack of correlation between K-ras point mutations and clinicopathological features (except histological type) supports the hypothesis of a random activation of the K-ras gene in human neoplastic endometrium.

Aged↗
PubMed1998

Sialic acid concentration in serum and tissue of endometrial cancer patients.

Serum total sialic acid (TSA) level was determined in the group of 45 patients with endometrial neoplasia. Moreover, the sialic acid content in 23 surgically obtained tumor tissue specimens has been estimated. The mean value of serum total sialic acid level of the cancer patients (2.38 mmol/l) was significantly higher (P < 0.0001) than the sialic acid level in the control group (1.52 mmol/l). The elevation of serum total sialic acid level was associated with the burden of the tumor (2.30 mmol/l and 2.68 mmol/l for stages I and II + III, respectively). Tissue sialic acid content showed no significant differences between early and advanced clinical stage of the disease.

Adult↗
PubMed1998

Expression of ras p21 in the stromal cells of human neoplastic endometrium.

ras p21 proteins have been reported to take part in signal transduction through a cell membrane to the nucleus and they also play a crucial role in the process of carcinogenesis. Forty specimens of neoplastic endometrium, ten slides of normal endometrium and one case of uterine carcinosarcoma were investigated for ras p21 expression in the stromal cells by immunohistochemistry. Stromal cells expressed ras p21 protein in 13 out of 40 (33%) cases of neoplastic endometrium. These cells were randomly dispersed wound the glandular crypts of the endometrium and were also detected in the adjacent myometrium surrounding the cancer tissue. When cancers were grouped by surgical stage, ras p21 protein was detected in 11/22 (50%) of stage I, but only in 2/18 (11%) of stages II-IV according to FIGO. None of the stromal cells immunostained for p21 in normal endometrium or myometrium, however, a single case of carcinosarcoma expressed ras p21 within the stromal cells.

Aged↗
PubMed1998

[Tissue zearalenone concentration in normal, hyperplastic and neoplastic human endometrium].

Zearalenone (ZEA), a nonsteroidal mycotoxin with estrogen-like activity, is synthesized by molds (Fusarium) commonly contaminating poorly stored agricultural products and foodstuffs. Human ER binds ZEA and this is probable mechanism of its action, although their influence on target tissues seems to be weaker (80-160 less active) comparing to E2. Zea has been observed to possess tumor-promoting activity similar to that of estrogens and hypothetically can inducing proliferation and carcinogenesis in estrogen-dependent tissues. Nowadays, the questions are, if ZEA is present in human endometrium and whether concentrations of this mycoestrogen is associated with endometrial cell proliferation. Endometrial tissues specimens were collected from 49 women (endometrial adenocarcinoma n = 27, endometrial hyperplasia n = 11, normal proliferative endometrium n = 11). Mean tissue zearalenone concentration in 3 endometrial hyperplasia and 22 adenocarcinoma samples was 47.8 +/- +/- 6.48 and 167 +/- +/- 17.69 ng/ml respectively in contrary to normal endometrium where tissue mycoestrogen concentration was not detectable. In 8 cases of hyperplastic and 5 cases of neoplastic endometrial tissue specimens ZEA was not observed. Our findings confirm the presence of ZEA in hyperplastic and neoplastic endometrium and therefore this substance might be of importance in carcinogenesis.

Adenocarcinoma↗
PubMed1997

ras p21 immunohistochemical detection in human endometrial carcinomas.

Tissue samples of 40 patients with histologically confirmed endometrial cancer were analyzed immunohistochemically on paraffin-embedded specimens to detect ras p21 protein expression. The relationship between p21 protein expression and clinicopathological findings was also analyzed. The intensity and distribution of specific cytoplasmatic staining were evaluated semiquantitatively by counting the immunohistochemical H-score. ras p21 expression was found in 30 (75%) of 40 human endometrial carcinomas, regardless of the clinical stage of the disease. Positive immunostaining for p21 was noted in 68% of stage I-II and in all 8 of the advanced stages (III-IV according to FIGO) of endometrial carcinomas. Myometrial invasion was related to ras p21 immunostaining (p = 0.009), however, no correlation between histological findings and ras p21 expression was observed.

Adenocarcinoma↗
PubMed1997

Detection of K-ras mutations in cancerous lesions of human endometrium.

The many genetic changes associated with human carcinogenesis include the activation and/or inactivation of various genes. Polymerase-chain reaction and single-strand conformation polymorphism analysis [PCR-SSCP] was used to detect alterations at exon 1 of the K-ras gene in 20 lesions of human endometrium. Six cases of endometrial hyperplasia, 13 of endometrial carcinoma and one of endometrial metastasis of ovarian cancer were analyzed. Mutations at exon 1 of the K-ras gene were detected in two of 13 human endometrial carcinoma [15%]; both were histologically defined adenocarcinomas, stage Ib and stage IIa according to the FIGO. Alterations were also observed in the single case of endometrial metastasis of ovarian cancer. It is worthy of note that among the six women with hyperplasic endometrial lesions K-ras gene mutation were not reported. These data suggest that K-ras activation is rare in Polish women and when it does occur it is in cancerous, but not in precancerous, lesions of human endometrium.

Adult↗