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Approximately 15% of patients with endometrial cancer present with high-risk disease (HREC). Moreover, assessing the extent of lymphovascular space invasion (LVSI) may provide prognostic insight among patients with HREC. The aim of this study was to determine whether the extent of LVSI can serve as a prognostic factor in HREC. All cases of ESMO-ESGO-ESTRO 2016 classified HREC in the Danish Gynecological Cancer Database (DGCD) diagnosed from 2005 to 2012 were reviewed for the presence and extent of LVSI (categorized using a 3-tiered definition). We used the Kaplan-Meier analysis to calculate actuarial survival rates, both adjusted and unadjusted Cox regression analyses were used to calculate the proportional hazard ratio (HR). A total of 376 patients were included in our analysis. Among 305 patients with stage I/II HREC, 8.2% and 6.2% had focal or substantial LVSI, respectively, compared with 12.7% and 38.0% of 71 patients with stage III/IV HREC, respectively. Moreover, the estimated 5-yr recurrence-free survival rate was significantly lower among patients with substantial LVSI compared with patients with no LVSI for both stage I/II (HR: 2.8; P=0.011) and stage III/IV (HR: 2.9; P=0.003) patients. Similarly, overall survival was significantly lower among patients with substantial LVSI for both stage I/II (HR: 3.1; P<0.001) and stage III/IV (HR: 3.2; P=0.020) patients. In patients with HREC, substantial LVSI is an independent adverse prognostic factor for lymph node and distant metastases, leading to reduced survival. Thus, the extent of LVSI should be incorporated into routine pathology reports in order to guide the appropriate choice of adjuvant treatment.

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or ≥4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (≥4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.

Background. Tetranectin (TN), a tetrameric, plasminogen-binding protein, was reduced in the plasma of patients with cancer and appears extracellularly in 'stimulated' connective tissues, such as the proliferative, connective tissue response to carcinomas known as desmoplasia. Methods. Tissue samples from 37 patients with ovarian cancer were examined immunohistochemically for stromal and cellular TN. Plasma samples obtained before the primary surgery were quantitated for TN. The univariate log-rank test and the multivariate Cox proportional hazards regression model were used to analyze the prognostic function of the variables. Results. A significantly higher survival rate was found for patients with a low-stromal TN score and a high-plasma TN concentration, whereas the cellular TN score did not have any significance. A significant negative correlation was found between plasma TN and stromal TN ([R.sub.s] = - 0.36; P = 0.03). Independent significant correlations were found between stromal immunoreactivity for TN and tumor grade (R = 0.67; P = 0.03) and between plasma TN and tumor stage (R = - 0.29; P = 0.01). Conclusions. This study gives great expectations to TN as a useful parameter for prognostic evaluation of patients with ovarian cancer. According to the correlations, stromal TN may partly originate from plasma and enhance proteolytic degradation in the interstitial tissue, a process necessary for the spread and growth of cancer. Because plasma TN measurements are only valid when taken preoperatively, it is of great value that stromal TN immunoreactivity of stored tumor tissue can be used as a prognostic factor for ovarian cancer.

Mismatch repair (MMR) is important for repairing of nucleotide mismatches during DNA replication. Germline mutations in MMR genes are associated with hereditary non-polyposis colorectal cancer (HNPCC). Ovarian cancer occurs as part of the HNPCC phenotype, and so common variants in MMR genes are candidates for ovarian cancer susceptibility. We performed a large multicentre case–control study to investigate associations of common variations in MMR genes and ovarian cancer using a single nucleotide polymorphism (SNP) tagging approach. A total of 2570 controls and 1531 cases from three separate studies were genotyped for 44 tagging SNPs (stSNP) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2). Genotype frequencies were marginally different between cases and controls for PMS2 rs7797466 (P2df = 0.046) with a 1.17-fold (95% CI 1.03–1.33) increase in risk for each ‘a’ allele carried (P-trend = 0.013). Haplotype analysis of PMS2 also showed significant differences in frequencies between cases and controls (P7df = 0.005), with one haplotype accounting for most of the effect. There was also marginal evidence for a recessive protective effect with common homozygote as the baseline comparator for two SNPs—MSH6 rs3136245 (OR 0.67; 95% CI 0.46–0.98) and MSH3 rs6151662 (OR 0.28; 95% CI 0.08–0.91)—but the comparisons of genotype frequencies for these variants were not significant (P = 0.10 and 0.054). In conclusion, it is unlikely that common variants in MLH1, MLH3, PMS1, MSH2, MSH3 and MSH6 contribute significantly to ovarian cancer susceptibility. The observed association of PMS2 rs7797466 with ovarian cancer warrants confirmation in an independent study.