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.

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.

US-appearance of a Küttner tumour resembling a malignant lesion: US-histopathologic correlation.

We present a case of unilateral Küttner tumour in the right submandibular gland. Its clinical course and ultrasound features inclined us to include a malignant lesion in the differential diagnosis. US-histopathologic correlation explained the ultrasound appearance of the lesion.

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.

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.

Studies on activation of H3 histamine receptor: a mechanistic model.

The recognition and the activation mechanism of the H3 histamine receptor was studied based on quantum-chemical calculations. A mechanistic model proposed both for recognition and activation stage clarifies different properties of histamine and alpha-methylhistamine at the H3 receptor. Interaction with a hypothetical receptor sites leads to the opening of the intramolecular hydrogen bonding in histamine, whereas the alpha-methylhistamine remains in closed conformation.

[A case of coexistence of meningioma with intracranial aneurysm in a patient with ruptured aortal aneurysm]. / Przypadek wspólistnienia oponiaka i tetniaka sródczaszkowego u osoby z peknietym tetniakiem aorty.

Fifty-three-year-old woman was admitted to hospital with tetraplegia symptoms and died two hours later. Clinical diagnosis was: cerebral stroke, hypertension in anamnesis. Postmortem examination showed ruptured dissecting aneurysm of thoracic and abdominal segment of aorta, meningioma of right pontocerebellar angle and saccular aneurysm of left inferior, posterior cerebellar artery. The diagnostic difficulties and hypotheses of formation of multifocal of different changes are discussed.

Theoretical studies on molecular determinants for recognition at H3 histamine receptors.

The determinants for recognition at H3 histamine receptors are considered. Findings based on quantum-chemical calculations suggest that H3 histamine receptor is less hydrophilic than the H2. The form most likely to be recognized by the H3 receptor is an intramolecularly hydrogen-bonded form of alpha-methylhistamine. Receptor environment and hydration effects of active form of histamine analogs are of crucial importance.

[The structure of distracting-compressing stabilizers Dynastab DK intended for functional treatment of articular fractures]. / Budowa dystrakcyjno-kompresyjnych stabilizatorów Dynastab DK przeznaczonych do czynnosciowego leczenia zlaman stawowych.

The structure of the distracting-compressing stabilizers Dynastab DK intended for functional treatment of transarticular fractures is described. The stabilizers realize the idea of functional treatment of fractures outside the hospital bed making possible free moving around of the patient during the treatment. This has been made possible owing to building-in of a mechanical articulation imitating the physiological movement in the injured joint. The articulation in the stabilizer reduces also the load on the joint. In the stabilizers for the treatment of such fractures of the elbow joint and ankle joint the articulations are monoaxial (hinge-like). In the stabilizer for the treatment of the radiocarpal joint this is a hinge articulation making possible flexion in sagittal plane. In the stabilizer for knee fractures the movements in the injured joint are taken over by a mechanical articulation of special structure. The distracting-compressing action of the Dynastab DK stabilizers for the treatment of transarticular fractures is realized by the tension screw mechanism e.g. in the stabilizer for the treatment of knee joint fractures. In the case of stabilizers for ankle joint, radiocarpal joint and elbow joint this tension is provided by calibrated compressing springs.