CXCL12 expression by healthy and malignant ovarian epithelial cells

<p>Abstract</p> <p>Background</p> <p>CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.</p> <p>Methods</p> <p>Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves.</p> <p>Results</p> <p>Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival.</p> <p>Conclusion</p> <p>Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00052468">NCT00052468</a></p

Lymphatic density (LD; a) and blood vessel density (BD; b) in the myocardium

, LDs in the normal myocardium and the seven categorized stages. LD means the total number of D2-40+ lymphatics in 20 fields of view observed by light microscopy at ×200 magnification. The values of LD are 21.2 ± 6.2 in the normal myocardial tissue (Normal), 7.6 ± 4.2 in Stage I, 0 in Stage II, 0 in Stage III, 1.3 ± 1.5 in Stage IV, 22.3 ± 25.7 in Stage V, 29.7 ± 25.0 in Stage VI and 20.8 ± 13.4 in Stage VII. There is no statistical difference between LD values in Stages V, VI and VII. Statistical analyses were performed by Student's -test. * 0.0001; ** 0.05. , Blood vessel density (BD) in the normal myocardium and the seven categorized stages. BD means the total number of CD34+ blood vessels counted by the same methods as the value of lymphatic density. The values of BD are 2693.4 ± 197.0 in Normal, 1689.9 ± 640.7 in Stage I, 571.4 ± 478.3 in Stage II, 51.8 ± 30.5 in Stage III, 1430.8 ± 323.1 in Stage IV, 1292.7 ± 153.1 in Stage V, 509.9 ± 276.3 in Stage VI and 130.5 ± 83.8 in Stage VII. After the onset of myocardial infarction, the BD value decreased up to Stage III. The BD values increased in Stage IV compared with Stage III, but decreased with the advance of the healing process of infarcted lesion up to Stage VII. Statistical analyses were performed by Student's -test. * 0.001; ** 0.0001.<p><b>Copyright information:</b></p><p>Taken from "Lymphangiogenesis in myocardial remodelling after infarction"</p><p></p><p>Histopathology 2007;51(3):345-353.</p><p>Published online 01 Sep 2007</p><p>PMCID:PMC2366023.</p><p>© 2007 The Authors. Journal compilation 2007 Blackwell Publishing Limited.</p

Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

BACKGROUND Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols. METHODS A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death. RESULTS A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001). CONCLUSIONS Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification