Total tissue lactate dehydrogenase activity in endometrial carcinoma

Lactate dehydrogenase (LDH) is essential for continuous glycolysis necessary for accelerated tumor growth. The aim of this study was to reconsider if assay of total tissue activity of this enzyme could be useful as marker for endometrial carcinoma (EC). Activity of LDH was measured spectrophotometrically in homogenate supernatants of uterine tissue samples of 40 patients (10 normal endometria, 27 normal myometria, and 33 EC), including 30 matched pairs. Data obtained were analyzed in relation to clinical and histopathologic findings and compared with our previously published results on the tissue levels of the same enzyme in ovarian cancer and on the proteolytic activity of dipeptidyl peptidase III (DPP III) in EC (suggested biochemical indicator of this malignancy). Significantly increased (1.8-3.0 times; P < 1 x 10(-4)) LDH activity was observed in EC samples if compared with normal uterine tissues. This rise was not related to the clinicopathologic findings, however. In contrast to previous results on LDH in ovarian carcinomas, a significant rise in LDH activity was found already in grade 1 EC. Using the cutoff value of 1.06 U/mg, diagnostic sensitivity of 82%, specificity of 100%, and accuracy of 91% for total tissue LDH assay have been calculated. A correlation of tissue's LDH and DPP III activities was found, and their combined assay for EC showed increased diagnostic sensitivity (94%) and accuracy (96%)

Expression of Ki-67, P53 and Progesterone Receptors in Uterine Smooth Muscle Tumors. Diagnostic Value

Aim was to investigate expression of Ki-67, P53 and progesterone receptors (PR) in leiomyomas (LM), smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyosarcomas (LMS) and to establish possible usefulness of these three parameters in distinguishing between LM and STUMP, and STUMP and LMS. Retrospective study of 51 uterine smooth muscle neoplasm (16 LM, 18 STUMP, 17 LMS) technically acceptable for analyses from years 2002–2007 from Department of Gynecological and Prenatal Pathology, University Hospital Center Zagreb, Croatia. Immunohistochemical analysis of Ki-67, P53 and PR expression was performed. Every nuclei stained brown, regardless of shade intensivity, was considered positive. The interpretation of immunohistochemical staining was expressed as number of positive cells in 100 cell count in most active area of the slide. Non-parametric analysis of variance Kruskal-Walis test was performed. Ki-67 expression was negative in all LM and higher than 5% in 12/18 STUMP and 10/17 LMS. Significant differences were observed between LM and STUMP expression for Ki-67 (p=0.000), and LM and LMS expression for Ki-67 (p=0.000).There was no expression of P53 in LM, expression of P53 was found in 7/17 LMS and 5/18 STUMP. Expression of P53 was significant between LM and LMS (p=0.002), and between LM and STUMP (p=0.006). Expression of PR was found in 16/16 LM and 18/18 STUMP, 10/17 LMS did not show PR expression. Expression of PR was significant between LM and LMS (p=0.018) and STUMP and LMS (p=0.004). The findings of our study in concordance with other study results are helpful information establishing more diagnostic criteria and parameters for diagnosis in doubtful cases between three entities. Immunoassaying for Ki-67, P53 and PR are such parameters. The panel of their expression in specific case eases diagnosis

Razina hemoglobina u odgovoru na preoperativnu kemoiradijaciju u bolesnica s lokalno uznapredovalim rakom vrata maternice

Hemoglobin level is a very important prognostic factor in patients with gynecological carcinomas. Anemia in patients with cervical carcinoma occurs frequently and is due to the aggressive biological potential of a tumor as well as because of the poor response of patients to radiation therapy. Chemoradiation is a standard treatment followed by surgery in patients with locally advanced cervical carcinomas. Good overall results after such treatment, good quality of life, and almost no recidivism have established this method as a treatment of choice for patients with locally advanced cervical carcinomas. Sixty-four female patients with cervical carcinoma underwent neoadjuvant chemoradiation, followed by radical hysterectomy at the Department of Gynecologic Oncology, University Medical Center in Zagreb. The stages of the disease ranged from FIGO stage Ib1 to FIGO stage IIIa. Histopathological findings were squamous cell carcinoma and glandular carcinoma of the cervix. The ECOG performance status was graduated from 0 to 1. Neoadjuvant chemoradiation regimen included cisplatin (40 mg/m² once a week for 4 weeks) with concomitant radiotherapy (40 Gy total pelvic + brach therapy). Furthermore, the time interval between chemoradiation and surgery was evaluated. Response to chemoradiation therapy was observed, and the hemoglobin level and general conditions (according to the ECOG performance status) were evaluated. All the 64 patients had chemoradiation therapy prior to radical surgery. The median dosage at point A was 77.28 Gy and the median duration time of chemoradiation was 34.37 days. The time interval from chemoradiation to radical surgery was approximately 34.4 days. Hemoglobin levels decreased from 120.7 to 108.7 g/l at the end of concomitant chemoradiation. The mean tumor diameter was significantly decreased after neoadjuvant chemoradiation, and we classified the results after chemoradiation therapy as complete remission, partial remission, and stabilization of the disease, according to the WHO response criteria with respect to the size of a residual tumor. After chemoradiation and surgery, the hemoglobin level and long-term survival were evaluated. The correlation between the hemoglobin level and long-term survival after neoadjuvant chemoradiation and radical surgery in patients with different stages of cervical cancer was studied. We found that hemoglobin level could be a prognostic factor, but mostly, along with other prognostic factors, such as ECOG performance status, stage of the disease, dosage at point A, and interval between chemoradiation and surgery. However, we observed that the cellular types of tumor were of no significance.Razina hemoglobina važan je prognostički pokazatelj u odgovoru na zračenje bolesnica s ginekološkim malignomima. Anemija udružena s rakom vrata maternice česta je i pokazatelj je ne samo biološki agresivnijeg tumora već može biti i uzrokom slabijeg odgovora na zračenje. Kemoiradijacija je uobičajeni način liječenja bolesnica s lokalno uznapredovalim rakom vrata maternice s ciljem poboljšanja odgovora na liječenje i preživljenja. Operativni zahvat nakon neoadjuvantne kemoiradijacije smanjuje lokalni recidiv. U Zavodu za ginekološku onkologiju u razdoblju od 1/01 do 12/04 liječene su 64 bolesnice s rakom vrata maternice. Stadij bolesti određivao se prema FIGO-klasifikaciji (od Ib1-IIIa), patohistološki se radilo o pločastom i žljezdanom tipu raka vrata maternice, a opće stanje određivalo se prema ECOG-u (0-1). U svih bolesnica provedeno je vanjsko zračenje zdjelice u dozi od 40 Gy, a potom i unutarnje zračenje, 1 aplikacija LDR s Cezijem 137 u dozi od 35-38 Gy u točku A. Tijekom vanjskog zračenja bolesnice su primale 1x tjedno Cisplatinu u dozi od 40 mg/m2 ukupno 4x kao radiosenzibilizator. Nakon provedenog zračenja bolesnice su operirane (histerektomija s adneksektomijom uz resekciju forniksa vagine, a u nekih bolesnica učinjena je i zdjelična limfadenektomija). Za vrijeme zračenja pratili smo vrijednosti hemoglobina 1x tjedno kao i opće stanje koje smo stupnjevali prema ECOG-u. Sve bolesnice su prije operacije ozračene. Srednja doza u točku A bila je 77,2 Gy, prosječno vrijeme zračenja bilo je 34,37 dana. Vrijeme između završetka zračenja i operacije iznosilo je 34,4 dana. Razina hemoglobina i veličina tumora znatno su se smanjivali tijekom kemoiradijacije. Procjenu odgovora na kemoiradijaciju učinili smo na patohistološkom nalazu uklonjenog vrata maternice prema WHO podjeli kao potpuni odgovor (CR), djelomičan odgovor (PR) te stabilnu bolest (SD). Početna vrijednost hemoglobina te redovito praćenje razine hemoglobina tijekom kemoiradijacije pokazali su kako je veći postotak CR i PR u bolesnica s višim vrijednostima hemoglobina (>120 mg/L nasuprot <100 mg/L). Bazalne i kontrolne vrijednosti hemoglobina u bolesnica s lokalno uznapredovalim rakom vrata maternice koje su liječene kemoiradijacijom i operacijom pokazale su se kao dobar prognostički pokazatelj odgovora na primijenjeno liječenje. Ovaj pokazatelj mora se uzeti u obzir s ostalim kao što su: stupanj uznapredovalosti bolesti, histološka diferencijacija i opće stanje bolesnice

Digital morphometry of cytologic aspirate endometrial samples [Digitalna morfometrijska analiza citoloških uzoraka aspirata endometrija]

Unlike cervical cytology, morphological cytology criteria in the differential diagnosis of endometrium have not yet been clearly defined, and methods to allow for more precise evaluation of endometrium status have been searched for. The aim of the present study was to assess the value of morphometric nucleus analysis of cytologic aspirate endometrial samples in proliferative, hyperplastic and malignant endometrium by use of digital image analysis. Morphometric analysis was performed on archival cytologic aspirate endometrial samples (at least 10 per group) stained according to Papanicolaou (n=77) and May-Grünwald-Giemsa (MGG; n=80) with the following histopathologic diagnoses: proliferative endometrium, hyperplasia simplex, hyperplasia complex, hyperplasia complex atypica, and adenocarcinoma endometriodes endometrii (grade I, II and III). Interactive image analysis (nuclear area, convex area, perimeter, maximum and minimum radius, length and breadth, as well as nucleus form factor and elongation factor) was performed by use of the SFORM software (VAMSTEC, Zagreb) on at least 50 (Papanicolaou stain) and 100 (MGG stain) well preserved endometrial epithelial cell nuclei without overlapping, at magnification of ´1000. Statistical data analysis was done by use of the Statistica Ver. 6 statistical package. Multivariate analysis (ANOVA) distinguished malignant, hyperplastic and proliferative endometrium according to all morphometric variables with both staining methods (p0.05) from atypical hyperplasia, adenocarcinoma and proliferative endometrium only according to the nucleus form factor and elongation factor (Papanicolaou stain), whereas malignant and atypical hyperplastic endometrium (MGG stain) differed statistically significantly (p0.05). According to the cytologic staining method, morphometric parameters were considerably higher in MGG stained endometrial samples, reaching the level of statistical significance (p0.05) in the groups of hyperplasia simplex and complex, well differentiated adenocarcinoma (form factor) and atypical hyperplasia (elongation factor). A combination of cytomorphology and the morphometric variables assessed in this study can yield useful information on the cytologic state of endometrium, with special reference to the possible differentiation of the group of hyperplasia without atypia from the group of adenocarcinoma and atypical hyperplasia

Ovarian Cancer: PCD and Brain Metastases

Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistocemicaly, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2–3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur

Digital Morphometry of Cytologic Aspirate Endometrial Samples

Unlike cervical cytology, morphological cytology criteria in the differential diagnosis of endometrium have not yet been clearly defined, and methods to allow for more precise evaluation of endometrium status have been searched for. The aim of the present study was to assess the value of morphometric nucleus analysis of cytologic aspirate endometrial samples in proliferative, hyperplastic and malignant endometrium by use of digital image analysis. Morphometric analysis was performed on archival cytologic aspirate endometrial samples (at least 10 per group) stained according to Papanicolaou (n=77) and May-Grünwald-Giemsa (MGG; n=80) with the following histopathologic diagnoses: proliferative endometrium, hyperplasia simplex, hyperplasia complex, hyperplasia complex atypica, and adenocarcinoma endometriodes endometrii (grade I, II and III). Interactive image analysis (nuclear area, convex area, perimeter, maximum and minimum radius, length and breadth, as well as nucleus form factor and elongation factor) was performed by use of the Sform software (Vamstec, Zagreb) on at least 50 (Papanicolaou stain) and 100 (MGG stain) well preserved endometrial epithelial cell nuclei without overlapping, at magnification of ´1000. Statistical data analysis was done by use of the Statistica Ver. 6 statistical package. Multivariate analysis (ANOVA) distinguished malignant, hyperplastic and proliferative endometrium according to all morphometric variables with both staining methods (p0.05) from atypical hyperplasia, adenocarcinoma and proliferative endometrium only according to the nucleus form factor and elongation factor (Papanicolaou stain), whereas malignant and atypical hyperplastic endometrium (MGG stain) differed statistically significantly (p0.05). According to the cytologic staining method, morphometric parameters were considerably higher in MGG stained endometrial samples, reaching the level of statistical significance (p0.05) in the groups of hyperplasia simplex and complex, well differentiated adenocarcinoma (form factor) and atypical hyperplasia (elongation factor). A combination of cytomorphology and the morphometric variables assessed in this study can yield useful information on the cytologic state of endometrium, with special reference to the possible differentiation of the group of hyperplasia without atypia from the group of adenocarcinoma and atypical hyperplasia

Cytology of Cervical Intraepithelial Glandular Lesions

Cytological criteria for the identification of glandular intraepithelial lesions (GIL) have not yet been fully described, especially for the precursors of adenocarcinoma in situ (AIS), thus these lesions may frequently remain unrecognized. As most patients diagnosed with AIS or mild to moderate GIL (grades I, II) are free from clinical symptoms, cytology has a very responsible role in the detection of these lesions. The aim of the study was to achieve the most appropriate cytologic diagnosis of intraepithelial lesions of endocervical columnar epithelium, analyzing the cytology findings in patients with histologically verified AIS and GIL (I, II). The value of cytology in the detection and differential diagnosis was assessed in 123 patients with definitive histologic diagnosis of glandular lesions (AIS, n=13; GIL I, n=11; and GIL II, n=7), and glandular lesions associated with squamous component (AIS associated with cervical intraepithelial neoplasia (CIN) or invasive squamous cell carcinoma (SCC), n=58; GIL I or GIL II associated with CIN, n=28; and GIL associated with microinvasive squamous carcinoma (MIC), n=6). In 95.1% of patients, lesions were detected by cytologic analysis that indicated additional diagnostic procedure. In terms of differential diagnosis, cytology showed higher accuracy in predicting lesion severity vs. type of epithelial alteration (75.6% vs. 55.3%) and abnormalities of columnar epithelium (95.7%; vs. 74.2%). The accuracy of cytology was higher in pure (AIS, 61.5% and GIL I, II, 22.2%) than in mixed lesions (25.9% and 20.6%). Continuous improvement in cervical specimens and cytodiagnostic skills, better understanding of intraepithelial adenocarcinoma and precursors, and their inclusion in the classification of cytologic and histologic findings are expected to upgrade the detection of these lesions, and to reduce the invasive cervical adenocarcinoma morbidity and mortality

Expression of Ki-67, P53 and progesterone receptors in uterine smooth muscle tumors. Diagnostic value [Ekspresija KI-67, P53 i progesteronskih receptora u glatkomišićnim tumorima maternice. Dijagnostička vrijednost]

Aim was to investigate expression of Ki-67, P53 and progesterone receptors (PR) in leiomyomas (LM), smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyosarcomas (LMS) and to establish possible usefulness of these three parameters in distinguishing between LM and STUMP, and STUMP and LMS. Retrospective study of 51 uterine smooth muscle neoplasm (16 LM, 18 STUMP, 17 LMS) technically acceptable for analyses from years 2002–2007 from Department of Gynecological and Prenatal Pathology, University Hospital Center Zagreb, Croatia. Immunohistochemical analysis of Ki-67, P53 and PR expression was performed. Every nuclei stained brown, regardless of shade intensivity, was considered positive. The interpretation of immunohistochemical staining was expressed as number of positive cells in 100 cell count in most active area of the slide. Non-parametric analysis of variance Kruskal-Walis test was performed. Ki-67 expression was negative in all LM and higher than 5% in 12/18 STUMP and 10/17 LMS. Significant differences were observed between LM and STUMP expression for Ki-67 (p=0.000), and LM and LMS expression for Ki-67 (p=0.000).There was no expression of P53 in LM, expression of P53 was found in 7/17 LMS and 5/18 STUMP. Expression of P53 was significant between LM and LMS (p=0.002), and between LM and STUMP (p=0.006). Expression of PR was found in 16/16 LM and 18/18 STUMP, 10/17 LMS did not show PR expression. Expression of PR was significant between LM and LMS (p=0.018) and STUMP and LMS (p=0.004). The findings of our study in concordance with other study results are helpful information establishing more diagnostic criteria and parameters for diagnosis in doubtful cases between three entities. Immunoassaying for Ki-67, P53 and PR are such parameters. The panel of their expression in specific case eases diagnosis

Razina hemoglobina u odgovoru na preoperativnu kemoiradijaciju u bolesnica s lokalno uznapredovalim rakom vrata maternice

Hemoglobin level is a very important prognostic factor in patients with gynecological carcinomas. Anemia in patients with cervical carcinoma occurs frequently and is due to the aggressive biological potential of a tumor as well as because of the poor response of patients to radiation therapy. Chemoradiation is a standard treatment followed by surgery in patients with locally advanced cervical carcinomas. Good overall results after such treatment, good quality of life, and almost no recidivism have established this method as a treatment of choice for patients with locally advanced cervical carcinomas. Sixty-four female patients with cervical carcinoma underwent neoadjuvant chemoradiation, followed by radical hysterectomy at the Department of Gynecologic Oncology, University Medical Center in Zagreb. The stages of the disease ranged from FIGO stage Ib1 to FIGO stage IIIa. Histopathological findings were squamous cell carcinoma and glandular carcinoma of the cervix. The ECOG performance status was graduated from 0 to 1. Neoadjuvant chemoradiation regimen included cisplatin (40 mg/m² once a week for 4 weeks) with concomitant radiotherapy (40 Gy total pelvic + brach therapy). Furthermore, the time interval between chemoradiation and surgery was evaluated. Response to chemoradiation therapy was observed, and the hemoglobin level and general conditions (according to the ECOG performance status) were evaluated. All the 64 patients had chemoradiation therapy prior to radical surgery. The median dosage at point A was 77.28 Gy and the median duration time of chemoradiation was 34.37 days. The time interval from chemoradiation to radical surgery was approximately 34.4 days. Hemoglobin levels decreased from 120.7 to 108.7 g/l at the end of concomitant chemoradiation. The mean tumor diameter was significantly decreased after neoadjuvant chemoradiation, and we classified the results after chemoradiation therapy as complete remission, partial remission, and stabilization of the disease, according to the WHO response criteria with respect to the size of a residual tumor. After chemoradiation and surgery, the hemoglobin level and long-term survival were evaluated. The correlation between the hemoglobin level and long-term survival after neoadjuvant chemoradiation and radical surgery in patients with different stages of cervical cancer was studied. We found that hemoglobin level could be a prognostic factor, but mostly, along with other prognostic factors, such as ECOG performance status, stage of the disease, dosage at point A, and interval between chemoradiation and surgery. However, we observed that the cellular types of tumor were of no significance.Razina hemoglobina važan je prognostički pokazatelj u odgovoru na zračenje bolesnica s ginekološkim malignomima. Anemija udružena s rakom vrata maternice česta je i pokazatelj je ne samo biološki agresivnijeg tumora već može biti i uzrokom slabijeg odgovora na zračenje. Kemoiradijacija je uobičajeni način liječenja bolesnica s lokalno uznapredovalim rakom vrata maternice s ciljem poboljšanja odgovora na liječenje i preživljenja. Operativni zahvat nakon neoadjuvantne kemoiradijacije smanjuje lokalni recidiv. U Zavodu za ginekološku onkologiju u razdoblju od 1/01 do 12/04 liječene su 64 bolesnice s rakom vrata maternice. Stadij bolesti određivao se prema FIGO-klasifikaciji (od Ib1-IIIa), patohistološki se radilo o pločastom i žljezdanom tipu raka vrata maternice, a opće stanje određivalo se prema ECOG-u (0-1). U svih bolesnica provedeno je vanjsko zračenje zdjelice u dozi od 40 Gy, a potom i unutarnje zračenje, 1 aplikacija LDR s Cezijem 137 u dozi od 35-38 Gy u točku A. Tijekom vanjskog zračenja bolesnice su primale 1x tjedno Cisplatinu u dozi od 40 mg/m2 ukupno 4x kao radiosenzibilizator. Nakon provedenog zračenja bolesnice su operirane (histerektomija s adneksektomijom uz resekciju forniksa vagine, a u nekih bolesnica učinjena je i zdjelična limfadenektomija). Za vrijeme zračenja pratili smo vrijednosti hemoglobina 1x tjedno kao i opće stanje koje smo stupnjevali prema ECOG-u. Sve bolesnice su prije operacije ozračene. Srednja doza u točku A bila je 77,2 Gy, prosječno vrijeme zračenja bilo je 34,37 dana. Vrijeme između završetka zračenja i operacije iznosilo je 34,4 dana. Razina hemoglobina i veličina tumora znatno su se smanjivali tijekom kemoiradijacije. Procjenu odgovora na kemoiradijaciju učinili smo na patohistološkom nalazu uklonjenog vrata maternice prema WHO podjeli kao potpuni odgovor (CR), djelomičan odgovor (PR) te stabilnu bolest (SD). Početna vrijednost hemoglobina te redovito praćenje razine hemoglobina tijekom kemoiradijacije pokazali su kako je veći postotak CR i PR u bolesnica s višim vrijednostima hemoglobina (>120 mg/L nasuprot <100 mg/L). Bazalne i kontrolne vrijednosti hemoglobina u bolesnica s lokalno uznapredovalim rakom vrata maternice koje su liječene kemoiradijacijom i operacijom pokazale su se kao dobar prognostički pokazatelj odgovora na primijenjeno liječenje. Ovaj pokazatelj mora se uzeti u obzir s ostalim kao što su: stupanj uznapredovalosti bolesti, histološka diferencijacija i opće stanje bolesnice