Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.

We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer.

Debulking metastatic pelvic nodes before radiotherapy in cervical cancer patients: a long-term follow-up result.

BACKGROUND: Enlarged pelvic nodes are commonly found during preoperative imaging studies in cervical cancer patients and may represent tumor metastasis. It remains controversial whether debulking of these enlarged nodes prior to definitive radiotherapy offers any survival benefit to the patient. METHODS: Enlarged suspicious pelvic nodes identified by imaging studies in stage 1B to stage IIA (early-stage) cervical cancer patients prior to scheduled radical hysterectomy and in stage 1B2 or above (advanced-stage) cervical cancer patients destined for radiotherapy were debulked. Patients with confirmed nodal metastasis (node-positive) were primarily treated by radiotherapy and patients with no evidence of nodal metastasis (node-negative) were treated as planned. Clinical outcomes of these two groups of patients are reported after a long-term follow-up. RESULTS: Sixteen of 110 early-stage and 37 of 97 advanced-stage cervical cancer patients had their enlarged metastatic nodes removed before they were treated by radiotherapy. Microscopic metastatic pelvic nodes were found in six additional patients after the radical hysterectomy and four of them received postoperative adjuvant radiotherapy. After a median follow-up of 62 months, the rates of recurrence inside the pelvis are not significantly different between node-positive and node-negative patients with both early-stage and advanced-stage disease. Recurrences outside the pelvis occurred in 59.1% early-stage and 44.8% advanced-stage node-positive patients, and were the primary cause of poor survival. CONCLUSIONS: Debulking enlarged metastatic pelvic nodes may help reducing pelvic recurrence but does not seem to benefit survival.

The technique of laparoscopic pelvic ultrasonography for metastatic lymph node.

Many reports have provided evidence to support the effective use of diagnostic laparoscopy and laparoscopic ultrasonography (LUS) to determine if patients with upper abdominal malignant diseases are operable so that unnecessary laparotomy can be avoided. LUS is less frequently applied to patients with pelvic malignancies and this is probably related to the technical difficulties. We have developed the LUS technique in examining the pelvic nodes for metastasis systematically and have applied it to 241 cervical cancer patients. The procedure is safe and not associated with any major morbidity. The mean duration of pelvic node assessment by LUS is 14 minutes and the procedure can be satisfactorily completed in 98% of patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LUS in detecting pelvic nodal metastasis were 81.2%, 55.6%, 88.4%, 57.7%, and 87.5%, respectively, in patients scheduled for radical hysterectomy. In this report, we describe the LUS technique in detail and demonstrate important landmarks that provide useful orientation during an LUS examination. The technical limitations and pitfalls are also discussed.

Expression of maspin in endometrioid adenocarcinoma of endometrium.

Maspin is a member of the serpin family, whose expression is altered in neoplasia and malignancies of many tissues. Underexpression of maspin has been reported in breast and prostatic cancers, but in some cancers such as ovarian, colorectal and pancreatic carcinoma, it was found to be up-regulated. This study aimed at demonstrating the expression of maspin in human endometrial tissue and searching for any altered expression in endometrioid adenocarcinoma of the endometrium compared to normal endometrium. The expression level of the maspin gene was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) performed on RNA extracted from 34 endometrial cancer samples (including 24 with FIGO stage I disease and 10 with FIGO stage III disease) and 28 normal endometrium in proliferative or secretory phases. Immunohistochemical staining was also performed on 10 cases of endometrial cancer (6 FIGO stage I cases and 4 FIGO stage III cases) as well as 15 normal endometrium. Semi-quantitative RT-PCR revealed that the expression of maspin was significantly up-regulated in both stage I (p<0.01) and stage III (p<0.01) endometrial cancer compared with normal endometrium. However, no significant difference in maspin expression was demonstrated between stage I and stage III endometrial cancer. Immunostaining of all tissue sections revealed an immunopositive signal in the nuclei of the normal or cancerous endometrial glandular cells. In 60% of the cancer cases, cytoplasmic staining was also evident. Our results suggested that there is up-regulated expression of maspin in endometrioid endometrial adenocarcinoma. Cytoplasmic immuno-expression of maspin is common in endometrial cancer. It may play a role in the malignant transformation of human endometrial tissue.