High expression of mTOR is associated with radiation resistance in cervical cancer

Objective

Mammalian target of rapamycin (mTOR) is known to promote cell proliferation, survival, and resistance to radiation. The aim of this study was to determine whether mTOR expression was associated with survival and the response to radiation in patients with cervical cancer.

Methods

After reviewing 119 patients treated by primary radiotherapy for stage IIB-IVA cervical cancer, a case-control study was performed. The cases (n=12) with local recurrence or radiation failure after primary radiation therapy were selected. For each case, two controls that had no recurrence were selected. Using pretreatment paraffin-embedded tissues, the cytoplasmic expression of phosphorylated-mTOR (p-mTOR) was evaluated by immunohistochemistry. Staining was scored based on intensity (intensity score [IS] 0-3) and proportion (proportion score [PS] 0-100). The progression free survival (PFS) was defined from the end of treatment to the day of recurrence by imaging studies or biopsy. The staining distribution and PFS were compared between the two groups. The results were analyzed by the Student t-test, Mann-Whitney U-test, Fisher''s exact test, and Cox proportional hazards regression model.

Results

The p-mTOR cytoplasmic expression was significantly associated with a poor response to radiotherapy (p<0.01). With respect to survival, a higher cytoplasmic expression of p-mTOR was associated with a worse outcome (p=0.02). The hazard ratio for recurrence or radiation failure was 6.18 for mTOR IS and 1.04 for mTOR PS (p<0.05 for both), indicating that the degree of p-mTOR staining correlated with the recurrence risk.

Conclusion

High expression of p-mTOR was associated with radiation resistance; therefore p-mTOR may be a prognostic marker for response to radiotherapy in patients with cervical cancer.     

Survival benefit from ovarian metastatectomy in colorectal cancer patients with ovarian metastasis: a retrospective analysis

Purpose

A recent study demonstrated that colorectal cancer (CRC) with ovarian metastases was less responsive to chemotherapy compared with extraovarian metastases. Hence, the ovary may actually represent a “sanctuary” for metastatic cells from CRC. The aim of the study was to investigate the impact of ovarian metastatectomy on survival of CRC patients with ovarian metastasis.

Methods

Between 1996 and 2008, 83 CRC patients underwent an oophorectomy. For the historical control, 47 CRC patients with ovarian metastasis without resection were included in the analysis.

Results

The median age was younger (48 years) in the oophorectomy group compared with the historical control (54 years; P = 0.012). The proportion of synchronous metastasis was higher in the oophorectomy group than in the control group (57 vs. 30%; P = 0.003). After a median follow-up duration of 60.8 months (range of 7.4–169.7 months), the median OS was significantly longer in the oophorectomy group (28.1 vs. 21.2 months, oophorectomy vs. non-oophorectomy; P = 0.038). For ovary-specific survival (date of ovarian metastasis diagnosis to death), CRC patients with an oophorectomy showed a significantly more favorable survival rate than the control group (20.8 vs. 10.9 months; P < 0.001). In univariate analyses, oophorectomy (P = 0.038), unilaterality of ovarian metastasis (P = 0.032), metastasis confined to ovaries (P < 0.001), normal CEA level (P < 0.001), good performance status (P = 0.001), palliative chemotherapy (P = 0.001), and primary disease resection (P = 0.005) were identified as significantly good prognostic factors for overall survival. The oophorectomy, chemotherapy, metastasis confined to ovaries, normal CEA level, and good performance status retained statistical significance at the multivariate level (P = 0.003, P = 0.004, P = 0.005, P = 0.015, and P = 0.029, respectively).

Conclusions

Based on this retrospective analysis, the ovarian metastatectomy significantly prolonged survival in CRC patients with ovarian metastases. The potential role of an ovarian metastatectomy in the management of CRC should be prospectively studied.     

Ovarian Mass Mimicking Malignancy: A Case Report

A 32-year-old female who suffered from abdominal pain underwent ¹⁸F-fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the diagnostic workup of pelvic mass lesions. Cystic mass lesions in the bilateral ovaries showed wall thickening and intense hypermetabolism along the rim. In addition, multifocal intense hypermetabolic lymphadenopathies were seen in the left paraaortic lymph node (LN), aortocaval LN, and both common iliac LNs. We interpreted these findings as bilateral ovarian cancer with retroperitoneal metastatic lymphadenopathies rather than endometriosis with reactive lymphadenopathies. However, histopathological examination confirmed the ovarian mass lesions as tubo-ovarian abscesses. We report a case that even if simultaneous hypermetabolic retroperitoneal LNs are seen, intense hypermetabolic lesions in both ovaries can be in consequence of inflammatory change.     

Dynamin 2 expression as a biomarker in grading of cervical intraepithelial neoplasia

Objective

Dynamin 2, which plays a role in endocytosis, is known to be required for HPV infection on host cells. We investigated dynamin 2 as a biomarker in grading of cervical intraepithelial neoplasia (CIN) by comparing with Ki-67 expression and the type of HPV infection (low-risk vs. high-risk).

Study design

We performed immunohistochemical stains of dynamin 2 and Ki-67 on tumor samples of patients with CIN and the type of HPV infection was investigated.

Results

All the patients with reactive changes (n = 7) or normal (n = 4) did not show dynamin 2 expression. There were 33, 14, and 12 cases with CIN I, II, and III, respectively, and there was a negative correlation between the degree of dynamin 2 expression and the severity of CIN lesions with statistical significance (P < 0.001). Negative expression of dynamin 2 was more sensitive for the detection of CIN II/III than high expression (2+) of Ki-67 (96.2% vs. 73.1%, P = 0.041). Among patients in whom HPV infection was detected, the degrees of dynamin 2 expression were not associated with the type of HPV infection (low-risk vs. high-risk). Overall, there was a negative correlation between the expression patterns of Ki-67 and dynamin 2.

Conclusion

We found that dynamin 2 may be a helpful biomarker in grading of CIN lesions and a candidate biomarker for detecting low grade CIN with high sensitivity.     

Genetic profiling to predict recurrence of early cervical cancer

Objective

Recurrence is the major cause of death in early cervical cancer. We compared the prediction powers for disease recurrence between the gene set prognostic model and the clinical prognostic model.

Materials and methods

A gene set model to predict disease free survival was developed using the cDNA-mediated annealing, selection, extension, and ligation (DASL) assay data set from a cohort of early cervical cancer patients who had been treated with radical surgery with or without adjuvant therapy. A clinical prediction model was also developed using the same cohort, and the ability of predicting recurrence from each model was compared.

Results

Adequate DASL assay profiles were obtained from 300 patients, and we selected 12 genes for the gene set model. When patients were categorized as having a low or high risk by the prognostic score, the Kaplan–Meier curve showed significantly different recurrence rates between the two groups. The clinical model was developed using FIGO stage and post-surgical pathological findings. In multivariate Cox regression analysis of prognostic models, the gene set prognostic model showed a higher hazard ratio than that of the clinical prognostic model.

Conclusions

The genetic quantitative approach may be better in predicting recurrence in early cervical cancer patients.