Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer.

BACKGROUND: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma. METHODS: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial. RESULTS: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I-II disease (HR=2.9; 95% CI, 1.2-6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy. CONCLUSIONS: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment. IMPACT: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61-67. ©2016 AACR.

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway.

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone.

Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting.

OBJECTIVE: The objective of the study was to investigate the prognostic impact of deoxyribonucleic acid (DNA) ploidy in endometrial carcinoma in a routine diagnostic series as compared with a research series. STUDY DESIGN: We studied a population-based series of 363 endometrial carcinomas prospectively collected, with long and complete follow-up. The prognostic value of DNA ploidy was investigated in a routine diagnostic series (n=262) and compared with the results from a previous research series (n=101). RESULTS: The proportion of DNA aneuploid tumors was 21% in the research series and 25% in the routine diagnostic series (P=NS). In both series, DNA aneuploidy was significantly correlated to higher age at diagnosis, nonendometrioid subtype, and high histologic grade. Patients with DNA aneuploid tumors had significantly poorer survival, adjusted for established clinicopathologic prognostic factors. CONCLUSION: DNA ploidy estimation in endometrial carcinoma adds independent prognostic information in a routine diagnostic setting.

Diagnostic and prognostic markers for gastrointestinal stromal tumors in Norway.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. The diagnosis of GIST is based on histology together with a panel of immunohistochemical markers; the most important is KIT (CD117). A total of 434 cases of GISTs were confirmed by histology and immunohistochemistry, and incorporated into tissue microarrays. Validation of histological features as well as the prognostic value of two immunohistochemical biomarkers (p16 and L1) was assessed. High mitotic rate, large tumor size, nuclear atypia, and small bowel primary site were all validated as negative prognostic factors in GISTs. Expression of p16 was significantly correlated with unfavorable prognosis, whereas L1 expression was not.

[Treatment of patients with gastrointestinal stromal tumour with imatinib mesylate]. / Behandling med imatinibmesylat av pasienter med gastrointestinal stromal tumor.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most frequent mesenchymal tumour type of the digestive tract. Between 30 and 40% of patients have high-risk, malignant GIST with poor prognosis after surgery. Imatinib mesylate is a recently introduced KIT tyrosine kinase inhibitor with effect on metastatic GIST. We report our experience with imatinib mesylate in the treatment of GIST. MATERIAL AND METHODS: Nine patients diagnosed with GIST have received imatinib mesylate since August 2001. Eight patients had metastatic disease, one patient received adjuvant treatment. The patients were evaluated according to standard protocols for clinical performance, effect of treatment, and adverse effects. Tumour tissue was analysed for mutational status in KIT and PDGFRA. RESULTS: All patients with metastatic disease had palliative benefit; three had partial response and the remaining stable disease. The single patient receiving adjuvant treatment had no sign of recurrence. Side effects were mainly mild diarrhoea, nausea and vomiting. Seven patients had mutations in KIT exon 11, one in KIT exon 9, and one in PDGFRA exon 12. INTERPRETATION: The results demonstrate that imatinib mesylate is an effective drug that can stabilise and reduce disease in patients with advanced GIST.