GST isoenzymes in matched normal and neoplastic breast tissue.

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. The interindividual variation in the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and of 1,2-epoxy-3-(p-nitrophenoxy) propane (EPNP) with glutathione (GSH) by cytosolic glutathione S-transferases (GSTs) were investigated in human breast matched normal and tumor samples. The GSTA, GSTM, GSTP and GSTT isoenzymes from the crude extracts of matched breast normal and tumor tissues in terms of their immunological properties using western blotting were compared. In most of the samples, the GST activities were higher in the tumor than in the normal cytosolic fractions against both CDNB and EPNP. In the western blotting analysis, it was proved statistically that in normal and tumor epithelial cells, there was difference between GST pi and theta isoenzymes expressions (p0.05). In normal epithelium there was a stronger GST theta expression than in invasive tumor tissues (p=0.013). However, the stronger GST pi expression was observed in tumor epithelium than in normal epithelium in human breast cancers (p=0.000). We found the GSTP protein level and GST activities were higher in the breast tumor than in the normal cytosolic fractions against both CDNB and EPNP, thus implicating a certain biological importance.

Reproducibility of grading systems for endometrial endometrioid carcinoma and their relation with pathologic prognostic parameters.

The FIGO grading for endometrial endometrioid carcinomas is widely accepted. In 2000, a novel binary architectural grading system was suggested that divided endometrioid carcinomas into low- and high-grade tumors. We aimed to evaluate the interobserver reproducibility of the FIGO, the architectural binary, and nuclear grading systems and the correlation between these grading systems and pathologic prognostic factors for endometrial endometrioid carcinoma. Eighty-eight endometrial endometrioid carcinomas from hysterectomy specimens were reevaluated by two pathologists independently. Kappa values for the FIGO, the binary, and the nuclear grading systems were 0.65, 0.67, and 0.09, respectively. The reproducibility of the FIGO and the binary grading systems was similar and substantial. FIGO grade 1 (60.2%) patients were comparable to binary low-grade (63.6%) patients. Most of the FIGO grade 3 (83%) patients were binary high grade. FIGO grade 2 patients were distributed between binary low and high grades. The FIGO grade 1 and 2 cases judged to be of binary high grade had deep myometrial invasion, and more cases had vascular invasion in comparison with FIGO grade 1 and 2 cases judged to be of binary low grade. In uni- and multivariate analyses, both grading systems, depth of myometrial invasion, vascular invasion, cervical involvement, and stage had no effect on overall survival. But binary high grade and vascular involvement are adverse prognostic factors on recurrence-free survival. Binary high-grade patients can be assigned as high-risk patients.

Recurrent partial hydatidiform mole: a report of a patient with three consecutive molar pregnancies.

Hydatidiform mole (HM) is the most common form of gestational trophoblastic neoplasia and is characterized by atypical hyperplastic trophoblasts and hydropic villi. Recurrence of HM is extremely rare. Here, we report the case of a patient with three consecutive partial HMs without normal pregnancy. A 28-year-old woman with gravida 3, para 0, was referred to our hospital with a diagnosis of an invasive mole in December 2003. She had three consecutive molar pregnancies in 2000, 2001, and 2003. All three molar pregnancies were evacuated by suction curettage and the patient was followed by serial beta-human chorionic gonadotropin levels. All three moles were histologically confirmed as partial moles. In the first two molar events no additional treatment after evacuation was required, but in the last event, the beta-human chorionic gonadotropin levels increased and an invasive mole was suspected. Diagnostic workup ruled out an invasive mole and choriocarcinoma. Karyotypic analysis of the patient and her husband was normal. The patient required chemotherapy for treatment of persistent disease. Recurrent partial HM is a very rare clinical disorder. Repetitive molar pregnancy is not an indication for chemotherapy, but persistent disease does require chemotherapy.

Utility of MIB-1 and estrogen and progesterone receptor in distinguishing between endometrial stromal sarcomas and endometrial stromal nodules, highly cellular leiomyomas.

It is difficult to differentiate between an endometrial stromal nodule (ESN) and endometrial stromal sarcoma (ESS) in curettage specimen, and the recommended therapy of endometrial stromal neoplasm is hysterectomy. If we could discriminate ESS from ESN in curettage specimens, there would be an opportunity to treat ESN by local excision rather than by hysterectomy. We analyzed MIB-1 and estrogen and progesterone receptor (ER/PR) expression in a retrospective series of 8 ESSs, 7 ESNs, and 17 highly cellular leiomyomas obtained from hysterectomy specimens. ESSs expressed MIB-1 more frequently than ESNs (P < 0.05), and ESSs had a tendency to express ER less frequently than ESNs (P= 0.08). We observed that in spite of showing MIB-1 expression to some extent, highly cellular leiomyomas usually could not reach ESSs' level and frequency of MIB-1 expression in the current study. Although MIB-1 and ER appear to be promising markers in the differential diagnosis of ESSs, a larger study would be necessary to confirm their validity.

High-grade neuroendocrine carcinoma of the cervix. A case report.

Neuroendocrine tumor of the uterine cervix is a rare and aggressive malignancy. Despite controversial, multimodal treatment methods, prognosis and treatment outcomes are worst in advanced stages. We report an early-stage case treated with the multimodal approach. The nomenclature proposed for this tumor type in 1997 by the College of American Pathologists still has some points of discussion. As in our case some of the tumors cannot be defined exactly into small or large cell types, and this causes confusion at least for nomenclature purposes. A 'mixed' type for this tumor may be appropriate.

Primary choriocarcinoma of the uterine cervix in a postmenopausal patient: a case report.

BACKGROUND: Primary cervical choriocarcinoma seen in a postmenopausal patient is a very rare entity. CASE: Primary choriocarcinoma of the uterine cervix was diagnosed in a 54-year-old woman. She had admitted to our clinic with vaginal bleeding and had been postmenopausal for 1 year at the time of diagnosis. A cervical tumoral mass was seen in her pelvic examination and cervical biopsy revealed squamous cell carcinoma of the cervix. Pelvic examination under anesthesia was done and patient was accepted as FIGO Stage IIA. Type III hysterectomy with bilateral salphingoopherectomy and bilateral pelvic-paraaortic lymph node dissection was carried out. Postoperative pathological evaluation of the surgical specimen showed that case was a primary choriocarcinoma of the cervix. CONCLUSION: This is one of the few reported cases of cervical choriocarcinoma in a postmenopausal patient. The most appropriate theory for the development of this tumor is metaplastic differentiation of the tumor from another histologic type.

7-ethoxyresorufin O-deethylase (EROD) activity is not capable of reflecting the overall malignant potential of breast cancer tissue.

7-Ethoxylesorufin O-deethylase (EROD) (mainly catalyzed by cytochrome P450 (CYP) 1A1 and used as a marker for CYP 1A1) activity was measured in the breast tumor and surrounding tumor free (normal) tissues of 37 female breast cancer patients with infiltrating ductal carcinoma. About 11% of the tumor and normal breast tissue samples lacked the enzyme activity. Large interindividual variations in the activities of EROD were found in both tumor and normal tissues ranging from 0 to 283 and 0 to 801 fmol/mg/min, respectively. However, no significant difference was noted between the mean EROD activities of tumor and normal breast tissues. This tendency did not change with the stage and grade of the malignancy and menopausal status. No significant correlation was observed between the EROD activity and stage or grade of malignancy (p > 0.05). Thus, it appears that EROD activity is not capable of reflecting the overall malignant potential of breast cancer tissue.

Glutathione and lipid peroxidation levels in human breast tumors.

The levels of reduced glutathione (GSH) and lipid peroxidation (LP) of breast tumor and surrounding tumor free (normal) tissues of 39 breast cancer female patients with infiltrating ductal carcinoma and the relationship between these two parameters were investigated. Large interindividual variations in the levels of GSH and LP were found in both tumor and normal tissues. The mean GSH levels of tumors were significantly higher than those of normal tissues. This tendency did not change with the stage and grade (excluding grade 1) of the malignancy, menopausal status and chemotherapy treatment. No correlation was found between GSH level and stage or grade of malignancy (p > 0.05). However, although more than half of the tumor samples (23/39, 59%) had higher LP levels than their corresponding normal tissues, no significant difference was noted between the mean LP levels of tumor and normal tissues. This tendency did not change with the stage and grade of the malignancy, and menopausal status and chemotherapy treatment. No relationship was observed between the LP level and stage or grade of malignancy (p > 0.05). Overall, no association existed between the levels of GSH and LP in tumors (p > 0.05). These results reveal that the GSH, but not LP, could be a marker of breast malignancy and that the increase in GSH level is not sufficient to lower the LP level in human breast tumors.

Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue.

An investigation was made of ethoxyresorufin O-deethylase (EROD) activity, a cytochrome P450 (CYP) dependent enzyme mainly catalyzed by CYP1A1, glutathione S-transferase (GST) activity toward the substrates 1-chloro-2,4- dinitrobenzene (CDNB) and ethacrynic acid (EAA), reduced glutathione (GSH) levels, and antioxidant enzyme (AOE) activity namely catalase (CAT) and selenium- dependent glutathione peroxidase (Se-GPx) in tumor and surrounding tumor-free (normal) tissues in female breast cancer patients. Wide interindividual variations were found in the enzyme activities in both tumor and normal breast tissues. No significant differences were noted between mean EROD and CAT activities in tumor and normal breast tissues. The mean activities of CDNB GST, EAA GST and Se-GPx and GSH levels in tumor tissue were significantly higher than those in normal breast tissue. These results show that CYP, GST and AOE behave differentially in breast tumors.