[Two cases of endometrial stromal sarcoma (ESS) in which survival was prolonged by administration of MPA].

Endometrial stromal sarcoma (ESS) is very rare. It accounts for 0.5% of all uterine corpus malignant tumors and 10% of all malignant non-epithelial tumors. MPA is one effective hormonal treatment for ESS. We describe two cases in which patients with metastatic low-grade ESS lesions had prolonged survival with MPA therapy. Case 1 was a 50-year-old woman with a low-grade uterine endometrial stromal tumor who had been operated on at another hospital. She had been followed for three years. She had pelvis metastases with infiltration into the bladder, and pulmonary metastases. She had an incomplete response to chemotherapy. We initiated MPA therapy, which resulted in significant improvement in her metastatic lesions. Case 2 was a 58-year-old woman with stage Ic low-grade ESS who presented with abnormal uterine bleeding. Following surgery (TAH+BSO), MPA therapy was initiated and she had no recurrence. After 1 year and 7 months, she discontinued the MPA because it worsened her articular rheumatism. Her cancer recurred with pelvic and paraaortic lymph node metastasis. She was treated with chemotherapy, MPA and radiotherapy. Her metastases improved, and the patient has continued to survive on MPA therapy alone. These cases suggest that MPA might be an effective hormonal therapy for patients with low-grade ESS.

Utility of ovarian biopsy in pancreatic metastasis of high-grade serous ovarian carcinoma: A case report.

It is very rare that ovarian carcinoma metastasizes to the pancreas, and pathological diagnosis is required to confirm the primary site. The present study reported a 73-year-old woman with serous carcinoma of the ovary that metastasized to the tail of the pancreas. Metastasis was confirmed by pathological and immunohistochemical examination of a biopsy of the ovarian tumor, an endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic tumor and computerized tomography-guided paraaortic lymph node biopsy. A biopsy of the ovarian tumor is useful to make a precise diagnosis and to determine proper treatment when ovarian and pancreatic tumors are identified at the same time and the primary neoplasm is uncertain.

Letrozole as second-line hormonal treatment for recurrent low-grade endometrial stromal sarcoma: A case report and review of the literature.

Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS remains unclear. The present study reports a case of stage IC LGESS presenting with abnormal uterine bleeding, and also provides a review of the literature. Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA therapy was initiated; treatment was successful, but discontinued 19 months later due to disruptive side effects. A further 2 months later, the patient presented with recurrent disease and received chemotherapy. MPA treatment was restarted with a partial response. A second recurrence, 4 years later, presented with lung and para-aortic lymph node metastases. The patient responded to treatment with the aromatase inhibitor letrozole. The patient has since exhibited stable disease and remained free of symptoms for 7 years. This case suggests that aromatase-inhibitor treatment may be effective for recurrent LGESS as a second-line treatment.

Expression of the type I interferon receptor and the interferon-induced Mx protein in human endometrium during the menstrual cycle.

OBJECTIVE: To investigate the expression of the type I interferon receptor (IFNAR) and interferon-induced Mx protein (Mx) in normal human endometrium throughout the menstrual cycle. DESIGN: Prospective study. SETTING: Medical university in Japan. PATIENT(S): Thirty-seven normal endometrial tissues from fertile women who had undergone hysterectomies for reasons other than endometrial disease. INTERVENTION(S): IFNAR-1, IFNAR-2, MxA, and MxB gene expression was analyzed by reverse transcription-real-time quantitative polymerase chain reaction. Moreover, localization of IFNAR-1 and IFNAR-2 were studied by immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of IFNAR-1, IFNAR-2, MxA, and MxB. RESULT(S): Expression of IFNAR-2 gene was significantly increased in the menstrual and midsecretory phase as compared with in the proliferative phase. Immunohistochemistry for IFNAR-1 and IFNAR-2 revealed weak staining of glandular epithelium and weak staining of stromal cells during the proliferative phase. However, an intense immunohistochemical staining of IFNAR-2 was observed on the surface and basement membrane of glands in the secretory phase. There was no statistical difference between MxA and MxB gene expression throughout the menstrual cycle. CONCLUSION(S): Our results suggest that IFNAR and Mx are expressed in the human endometrium and that the expression of IFNAR is cyclically changed during the menstrual cycle.

Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase.

Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.

Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase.

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine the relationship between DPD, cell proliferation and TP expression in human endometrium. We examined DPD gene expression using reverse transcription-polymerase chain reaction, DPD protein levels using enzyme-linked immunosorbent assay, and DPD protein localization using immunohistochemistry in 58 normal endometria and 28 endometrial cancers. DPD gene expression was then related to the proliferating cell nuclear antigen index and to TP gene expression. DPD gene expression, which was correlated with DPD protein level, was relatively stable throughout various menstrual phases but was significantly elevated in postmenopausal status. It was significantly lower in endometrial cancer than in normal endometrium. Localization analysis revealed that DPD protein was located primarily in epithelial cells, but was also present in stromal cells. DPD gene expression correlated inversely with the PCNA index. TP gene expression pattern contrasted with that of DPD in postmenopausal and malignant endometrium. A high ratio of TP to DPD gene expression was significantly more frequent in endometrial cancer than in normal endometrium in any menstrual phase. DPD may act cooperatively with TP to affect cell function by maintaining the pyrimidine nucleotide pool balance in normal and malignant endometrium.

The proliferative activity of ovarian tumors of low malignant potential differs from that of ovarian carcinoma.

Ovarian tumors of low malignant potential (LMPs) are intermediate between adenomas and ovarian carcinomas (OCs); however, whether an LMP is a precursor of OC or is a unique type of tumor that will not progress to OC is still controversial. To gain better insight into the relationship between LMP and OC, we compared proliferative and apoptotic activity and tumor size in 50 cases of LMP and 27 cases of OC. We employed immunohistochemical staining with Ki-67 and apoptotic labeling was based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The average tumor size observed in mucinous LMP was significantly larger than that in mucinous OC (p = 0.014). In contrast, there was no difference in tumor size between serous OC and serous LMP. The average Ki-67 labeling index (LI) in mucinous OC was significantly higher than that in mucinous LMP (p = 0.028). There was no difference between serous OC and serous LMP in the Ki-67 LI. There was also no difference in apoptotic indeed (AI) between OC and LMP, irrespective of histological subtype. A significant positive relationship between the Ki-67 LI and tumor size was observed in mucinous LMP (R = 0.516, p = 0.0003). Interestingly, the Ki-67 LI was inversely correlated with tumor size in mucinous OC (R = 0.570, p = 0.0317). Significant positive correlations between Ki-67 LI and tumor size were observed in both serous LMP and serous OC (R = 0.707, p = 0.0488, R = 0.789, p = 0.0168, respectively). No association was seen between AI and tumor size in LMP and OC, irrespective of histological subtype. The different associations between proliferative activity and tumor size in the mucinous subtype of LMP and OC suggest that mucinous LMPs may not be precursors of mucinous OCs. In contrast, the similar associations of proliferative activity with tumor size in the serous subtype of LMP and OC suggest that serous LMPs may be precursors of serous OCs.

Immunohistochemical characterization of non-epithelial cells in spiradenoma.

Spiradenoma is unique with respect to the presence of a large number of non-epithelial cells, including S100 protein(+) cells, most of which are presumably Langerhans cells, in the parenchyma as shown in the published work. However, the characterization of these non-epithelial cells to date is insufficient. Immunohistochemistry of CD1a, CD3, CD4, CD8, CD56, CD68, intercellular adhesion molecule-1 (ICAM-1), and HLA-DR, as well as double-immunofluorescence labeling of S100 protein/CD1a and CD1a/CD3, was performed using paraffin-embedded specimens from five cases of spiradenoma retrospectively. Non-epithelial cells evenly distributed throughout the parenchyma of spiradenoma primarily consisted of CD1a(+) Langerhans cells and CD3(+) T cells. ICAM-1 was expressed by epithelial cells and non-epithelial cells in the parenchyma. HLA-DR on the epithelial cells was limited to the focal area. In double-immunofluorescence labeling, approximately one-half of Langerhans cells were spatially related to T cells in the parenchyma, suggesting their functional interaction.

Clinical significance of interleukin-1 receptor antagonist in patients with cervical carcinoma.

OBJECTIVE: Our purpose was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1ra), which is an endogenous inhibitor cytokine of IL-1, in patients with cervical carcinoma. METHODS: Tissue IL-1ra expression and serum IL-1ra level were examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry in normal controls and patients with cervical carcinoma. RESULTS: Tissue IL-1ra protein level by ELISA was significantly higher in squamous cell carcinoma (n = 9) than in the normal cervix (n = 7) and adenocarcinoma (n = 3). Western blotting confirmed the main presence of intracellular IL-1ra type 1 in squamous cell carcinoma. Immunohistochemistry demonstrated significant IL-1ra expression only in tumor cells of squamous cell carcinoma. Elevation of serum IL-1ra level was found in patients with squamous cell carcinoma (n = 38) compared to normal women (n = 13), but not in patients with adenocarcinoma (n = 9). Although serum IL-1ra level did not correlate with clinical stage or any other tumor marker, high serum IL-1ra level was associated with pelvic lymph node metastasis and poor prognosis in patients with squamous cell carcinoma. On the other hand, these results were not obtained in patients with cervical adenocarcinoma. CONCLUSION: IL-1ra may play important roles in local and general malignant behaviors in patients with cervical squamous cell carcinoma, and measurement of serum IL-1ra level may be useful in predicting patient survival.