Uterine tumors resembling ovarian sex cord tumors: a case report with adenomyosis and complex hyperplasia with atypia.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are very rare uterine neoplasms. They mostly behave in a benign fashion but cases were reported with extra-uterine spread. There are less than 50 cases reported in the literature so far according to the present authors' knowledge. We report a case of 45-year-old woman with UTROSCT concurrent with adenomyosis and complex hyperplasia with atypia of endometrium and her three-year follow up.

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.

Thyroid cancer in toxic and non-toxic multinodular goiter.

BACKGROUND: Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG) than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. AIM: To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. SETTINGS AND DESIGN: Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. MATERIALS AND METHODS: We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. STATISTICAL ANALYSIS USED: Significance of the various parameters was calculated by using ANOVA test. RESULTS: The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. CONCLUSIONS: The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

Expression of gelatinase (MMP-2 and MMP-9) and cyclooxygenase-2 (COX-2) in endometrial carcinoma.

OBJECTIVE: Matrix metalloproteinases (MMPs) are key players in the degradation of extracellular matrix and basement membranes, and are thus important in tumor invasion. Gelatinases (MMP-2 and MMP-9) in particular are prognostic factors in many solid tumors. In this study the immunohistochemical expression of both COX-2 and matrix metalloproteinases has been shown for the first time in endometrium carcinoma. METHODS: Forty-two endometrial carcinoma tissues were immunostained for MMP2 antibody (1:100, Rabbit polyclonal), MMP9 antibody (1:100, Rabbit polyclonal) and CoX2 antibody (1:100, Epitope specific rabbit antibody). RESULTS: 90.5% of the cases were positive for MMP-2 and MMP-9, and 83.3% of the cases were positive for COX-2. A statistically significant association was found between COX-2 overexpression and FIGO stage (p = 0.001). A positive correlation was also found with histological grade (p = 0.006), myometrial invasion (p = 0.033), vascular invasion (p = 0.017), and lymphatic invasion (p = 0.007). A positive correlation was found between MMP-2 overexpression and vascular and lymphatic invasion (p = 0.030 and p = 0.003, respectively). MMP-9 overexpression was also found to be correlated with vascular and lymphatic invasion (p = 0.001 and p = 0.012, respectively). Furthermore, there was a statistically significant correlation between MMP-2 and MMP-9 overexpression (p = 0.0001). CONCLUSION: The results showed that COX-2, MMP-2 and MMP-9 were expressed in a high percentage of primary endometrial carcinomas and their expressions may be associated closely with parameters of tumor aggressiveness.

CD24 expression is a poor prognostic marker in endometrial carcinoma.

OBJECTIVE: CD24 is a cell adhesion molecule that has been implicated in metastatic tumor progression of various solid tumors. Its expression is known to be related to the prognosis of several kinds of tumors. This study was designed to examine the prognostic significance of CD24 in endometrial cancer patients. METHODS: Forty-four endometrial carcinoma tissues were immunostained for CD24 antibody (Ab2, clone 24 C02). Cytoplasmic and membranous immunoreactivity were scored semiquantitatively by Fisher's exact test. RESULTS: CD24 expression was detected in 34 (77.3%) out of 44 cases. Membranous and cytoplasmic staining of CD24 was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) grade (p = 0.011 and p = 0.002, respectively) and nodal status (p = 0.002 and p = 0.000, respectively). CONCLUSION: Our data suggests that CD24 expression in endometrial carcinoma as detected by immunohistochemistry might be a new marker for a more aggressive endometrial cancer biology. CD24 is commonly up-regulated in endometrial cancer and this corroborates the importance of CD24 in tumor progression among these cases.

Mucinous adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary--case report.

Benign cystic teratoma of the ovary (BCTO) is the most common ovarian germ cell tumor occurring predominantly in early adulthood. Malignant transformation of a BCTO is rare, with an incidence of 2%. Most benign cystic teratomas with malignant transformations are squamous cell carcinomas with just 6.8% being adenocarcinomas. We present a rare case of adenocarcinoma arising from the gastrointestinal epithelial elements of BCTO based on the microscopic examination and immunohistochemical studies. Adenocarcinoma arising from gastrointestinal epithelium within BCTOs is extremely rare. This is the fifth reported case of adenocarcinoma arising in gastrointestinal epithelium of a BCTO.

Comparison of NAT1, NAT2 and GSTT2-2 activities in normal and neoplastic human breast tissues.

In this study, arylamine N-acetyltransferases, NATs (E.C.2.3.1.5) and glutathione-S-transferase-T2-2, GSTT2-2 (E.C.2.5.1.18) enzyme activities in the breast tumor and surrounding tumor-free tissues of 22 female breast cancer patients with infiltrating ductal carcinoma were measured. The possible impacts of grade of malignancy, chemotherapy treatment, estrogen receptor status and menopausal status on all enzyme activities were evaluated. The results showed that, both NAT2 and GSTT2-2 display significant differences between tumor and tumor-free breast tissues, while no difference was observed in NAT1. Grade of malignancy seems to be positively associated with NAT1 and negatively associated with GSTT2-2. Though, both NAT2 and GSTT2-2 have increased mean tumor activities, the grade of malignancy, chemotherapy status, menopausal status or estrogen receptor status are not correlated statistically.

The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue.

Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 (CYP) enzymes play a major role in the activation of these chemicals. Using highly specific and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. the expression profile of all major xenobiotic metabolizing CYP forms was screened in breast tumour and surrounding tumour free (control) breast tissue in a series of 20 sample pairs obtained from females with infiltrating ductal carcinoma. The levels of CYPIAI mRNA were very low in both tumour and normal tissue. CYP1B1, CYP2B6, CYP2C, CYP2D6, CYP2E1, CYP4B1, and CYP11A1 expressions were positive in both tumours and control tissue. CYP2A6, CYP2A7, CYP2A13, CYP2F1, CYP3A4, CYP3A5. and CYP3A7 mRNAs were expressed neither in tumours nor in control tissue. These results show that several CYPs. responsible for the activation of a quite large number of procarcinogens and genotoxic estrogen metabolites. are expressed in breast tissue with a lack of qualitative differences in CYP expression at mRNA level between breast tumours and surrounding normal breast.

Lymphatic mapping and sentinel lymphadenectomy in early stage breast carcinoma.

The rate of axillary lymph node metastases is low in early stage breast carcinoma and axillary lymph node dissection is controversial in the treatment of these patients. Intraoperative lymphatic mapping technique is suggested for the identification of metastatic lymph nodes. Intraoperative lymphatic mapping was performed on 60 clinical stage I and II patients who were treated at Ankara Oncology Hospital between 1996-1998. Patent blue dye was injected in all cases, as the tumor was totally excised before mastectomy, into the surrounding breast tissue at four different quadrants. Presence of metastases were examined on stained lymph nodes (sentinel lymph node: SLN) by frozen-section. Modified radical mastectomy was performed including level I, II, III lymph node dissection. Metastases were evaluated on the remnants of frozen-section tissues and unstained lymph nodes (nonsentinel lymph node: nSLN) in axilla on hematoxyline-eosin stained slides and by immunohistochemistry. Forty-nine (81.6%) SLNs were identified among 60 cases. In 18 (36.7%) of these 49 patients, metastases were detected in SLNs by frozen section. In one case micrometastasis was detected in the remnants of frozen-section by immunohistochemistry though it was negative with hematoxyline-eosin. There were no metastases in nSLNs of 27 cases whose SLNs's frozen-sections were tumor free. In 3 cases SLNs were negative but metastases were detected in nSLNs (false negative: 6.1%). There were no local or systemic complications due to injections of dye. Selective lymph node dissections can be performed on early stage breast cancer patients by means of lymphatic mapping. This minimally invasive technique identifies metastatic axillary lymph nodes with a high degree of accuracy, so we can suggest that, non-metastatic patients can be treated without axillary dissection.

Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas.

Bcl-2 and Bax proteins are coded by a family of genes that take part in the manteinance of the balance between cell proliferation rate and programmed cell death in multicellular organisms. The Bax gene acts as promoter of cell death by opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2 and Bax proteins has been investigated in 58 cases of duct carcinoma in situ (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast. While both proteins were expressed at the same time in normal and benign epithelium, different staining patterns were observed according to the degree of differentiation of the neoplastic epithelium. In well-differentiated DCIS and grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly Bax protein staining pattern. Therefore, it appears that Bax protein expression, especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein expression is associated with less aggressive malignant lesions.

The effects of chemotherapy on breast cancer tissue in locally advanced breast cancer.

It is well known that chemotherapy induces cytomorphological changes in neoplastic and non-neoplastic tissue. Thirty-one stage III breast-carcinoma patients, treated with both pre-operative chemotherapy and mastectomy, were evaluated to define the effects of systemic chemotherapeutic agents in tumours, non-neoplastic breast tissue, and lymph nodes. Histological changes were compared with those observed in patients who had been treated by surgery alone. Cytoplasmic vacuolization was the most striking change in the tumour cells (59%). Chemotherapy was especially effective in the terminal duct lobular unit in non-neoplastic breast tissue. Lobular atrophy was observed in 20 (65%) cases, and lobular cellular atypia was seen in 16 (52%). The rate of ductal cellular atypia (42%) was not different from the control group. The most important changes seen in the non-neoplastic stromal component were fibrosis and hyalinization. These were found in 31 out of 727 evaluated lymph nodes. In serial sections, metastatic deposits were seen in or around these fibrotic or hyalinized areas. Chemotherapy is widely used in the treatment of early and locally advanced breast carcinomas. Familiarity with chemotherapy induced changes in breast tissue and lymph nodes have considerable importance in the accurate interpretation of these specimens.

Locally advanced breast cancer.

In vitro studies suggest p53 and bcl-2 may be important in the apoptotic response to irradiation, and that rapidly proliferating cells are more sensitive to radiotherapy. The clinical relevance of biological factors in predicting radiotherapy response was investigated in 62 patients with locally advanced breast cancer. Immunocytochemical staining for p53 protein, BCL-2 protein and MIB 1 antigen on the primary tumour, showed that none of these factors significantly predicted radiotherapy response (BCL-2 p=0.45, p53 p=1.0, MIB 1 p=0.92) and appear to be of no clinical value. A semi-quantitative assessment of MIB 1 staining showed a reduction in positive cells following radiotherapy (p=0.04), consistent with a reduced proliferation associated with response.