Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer.

AIM: Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study was designed to evaluate the role of HE4 in chemo-response against anti-cancer drugs and prognosis of epithelial ovarian cancer. METHODS: HE4-depleted cells and HE4-overexpressing cells were generated. The effect of HE4 gene silencing and overexpression was examined using a cell viability assay after exposure to chemotherapeutic agents and the signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H-score. RESULTS: Knockdown of HE4 in OVCAR-3 cells resulted in reduction in cell growth and increased sensitivity to paclitaxel and cisplatin compared to control cells. This effect originated from the decreased activation of cell-growth-related signaling, such as AKT and Erk mediated by epidermal growth factor (EGF), while overexpression of HE4 resulted in enhanced cell growth and suppressed the anti-tumorigenic activity of paclitaxel. Activation of AKT and Erk pathways was enhanced in HE4-overexpressing cells compared to control cells. Based on the results of multivariate analysis, the risk of death was significantly higher in patients with an H-score > 4. CONCLUSION: HE4 induces chemoresistance against anti-cancer drugs and activates the AKT and Erk pathways to enhance tumor survival. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients.

Effect of number of retrieved lymph nodes on prognosis in FIGO stage IB-IIA cervical cancer patients treated with primary radical surgery.

AIM: In the treatment of cervical cancer, the extent of lymphadenectomy is a matter of debate. The goal of the current study was to examine the question of whether the number of retrieved lymph nodes (RLN) can influence survival of patients with early stage cervical cancer. METHODS: The medical records of 180 FIGO stage IB-IIA cervical cancer patients treated with primary radical surgery were reviewed. Patients were divided into two groups: those with ≤ 40 RLN and those with > 40 RLN. Patients were also assigned to either the bulky (tumor size > 4 cm) cervical cancer group or the non-bulky (tumor size ≤ 4 cm) cervical cancer group. RESULTS: The number of RLN had a statistically significant effect on both disease-free survival (P = 0.04) and overall survival (P = 0.02) of all patients. Patients with > 40 RLN had better prognoses than those with ≤ 40 RLN. In the bulky cervical cancer group, the number of RLN was an independent prognostic factor. In multivariate analysis for the bulky cervical cancer group, > 40 RLN had a significant positive effect on disease-free survival (adjusted hazard ratio, 0.36; 95% confidence interval, 0.13-0.97) and overall survival (adjusted hazard ratio, 0.23; 95% confidence interval, 0.06-0.90). However, number of RLN was not an independent prognostic factor in the non-bulky cervical cancer group. CONCLUSIONS: A more extensive lymphadenectomy increased the survival of bulky cervical cancer patients. This finding may be helpful in determining surgical extent before surgery for cervical cancer.

Intraabdominal abscess caused by actinomycosis in a patient with mesenteric fibromatosis of the small intestine: report of a case.

A 38-year-old man presented to our Emergency Department with acute severe abdominal pain; 3 days after, a mesenteric mass had been detected by abdomino-pelvic computed tomography. Emergency laparotomy revealed a mesenteric mass with focal surface rupture. Microscopically, the mesenteric mass was composed of fibroblast-like spindle cells with intervening marked collagen deposits. These spindle cells were positive for nuclear ß-catenin and negative for CD34, c-kit, smooth muscle actin, and S-100 protein. We diagnosed the mesenteric lesion as deep fibromatosis, consistent with mesenteric fibromatosis (MF). Serial sections of the ruptured portion showed abscess formation with a peripheral radiating pattern of microcolonies, proven to be actinomycosis by Grocott's methenamine silver stain and gram staining. One glandular fragment was found in the adhered muscle layers and a foreign body reaction was seen within the abscess cavity. We speculate that MF involved the serosal adhesions between the adjacent bowel walls and the subsequent fibrous pulling might have created the connection between the bowel lumen and the bowel wall. This disrupted barrier led to the Actinomyces infection. To our knowledge, this is the first report of sporadic MF leading to the formation of an abscess cavity with rupture and actinomycosis.

Ovarian malignant melanoma without evidence of teratoma.

A 46-year-old woman with ovarian malignant melanoma had advanced intraperitoneal metastasis, retroperitoneal and inguinal lymph node metastases. Extensive debulking surgery was performed and chemotherapy was given. Microscopically, no evidence of other accompanying tumor, such as teratoma was noted. Detailed examination of the patient failed to identify any evidence of another primary melanoma site. It is assumed that spontaneous regression of the primary lesion occurred. Despite the surgery and chemotherapy, the patient died within 2 months of diagnosis. Considering this case, it is assumed that the combination of surgical debulking and chemotherapy are not always beneficial in ovarian malignant melanoma and the prognosis of ovarian malignant melanoma is very poor.

Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45.

A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen.

A case of ovarian steroid cell tumor, not otherwise specified, treated with surgery and gonadotropin releasing hormone agonist.

Steroid cell tumors account for less than 0.1% of all ovarian tumors. There are three steroid cell tumor subtypes: steroid cell tumor not otherwise specified (NOS), stromal luteoma and Leydig cell tumor. Steroid cell tumor, NOS, is the most common type and has malignant potential. This report describes a case of an ovarian steroid cell tumor, NOS. A 35-year-old woman visited hospital with the complaint of metrorrhagia. Physical examination revealed increased pubic hair. Transvaginal ultrasound indentified a 4.9 × 3.4 cm, well-circumscribed and solid left ovarian tumor. After laparoscopic left oophorectomy, the tumor was revealed as an ovarian steroid cell tumor, NOS. During the laparoscopic surgery, tumor ruptured. Complete surgical staging was performed and no evidence of metastasis was found. Gonadotropin releasing hormone agonist was administered monthly for 6 months. The patient has had no evidence of recurrence for 43 months.