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Protein expression of Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) has been identified as a prognostic factor in lymph-node negative (LN-) breast cancer patients. We aim to validate MARCKSL1 protein expression as a prognostic marker for distant metastasis-free survival (DMFS) in a new cohort of LN- breast cancer patients. MARCKSL1 expression was evaluated in 151 operable T1,2N0M0 LN- breast cancer patients by immunohistochemistry. Median follow-up time was 152 months, range 11–189 months. Results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation) using single (Kaplan-Meier) and multivariate (Cox model) survival analysis. Thirteen patients (9%) developed distant metastases. With both single and multiple analysis of all features, MARCKSL1 did not show a significant prognostic value for DMFS (p = 0.498). Of the assessed classical prognosticators, only tumor diameter showed prognostic value (hazard ratio 9.3, 95% confidence interval 2.8–31.0, p <0.001). MARCKSL1 expression could not be confirmed as a prognostic factor in this cohort. Possible reasons include changes in diagnostic and treatment guidelines between the discovery and validation cohorts. Further studies are needed to reveal the potential biological role of this protein in breast cancer. [ABSTRACT FROM AUTHOR]

Gudlaugsson E, Skaland I, Janssen E A M, Smaaland R, Shao Z, Malpica A, Voorhorst F & Baak J P A (2012) Histopathology Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer Aims: The proliferation factor Ki67 is prognostic in breast cancer and included in international therapy guidelines, but measurement procedures differ between laboratories. We compared the reproducibility and prognostic value of different Ki67 sampling and measurement methods. Methods and results: In 237 T1,2N0M0 breast cancers without adjuvant systemic treatment, strictly standardized section thickness, automated antigen retrieval and immunohistochemistry were used. The percentages of Ki67-positive nuclei were assessed using (i) a 'quick-scan rapid estimate', (ii) ocular-square-guided counts by independent pathologists, (iii) computerized point-grid-sampling interactive morphometry (CIM) and (iv) automated digital image analysis (DIA). Quick-scan rapid estimates were poorly reproducible. The optimal prognostic thresholds of Ki67 counts by two pathologists differed greatly (4%, 14%; kappa: 0.36), with many therapeutic differences. CIM-Ki67 and DIA-Ki67 were strongly prognostic ( P < 0.0001) and reproducible. DIA-Ki67 (threshold: 6.5%) was the strongest and most robust prognosticator (the threshold could vary from 4 to 15% without significant prognostic loss). Ki67 was prognostically strongest in the periphery of the tumour. Conclusion: In node-negative breast cancer without adjuvant systemic treatment, Ki67% by DIA, but not subjective counts, is reproducible and prognostically strong. This casts serious doubt on therapeutic guidelines using subjective counts of Ki67. [ABSTRACT FROM AUTHOR]

Background. Traditional Chinese herbal medicine was associated with improved prognosis in patients with performance score 0-1 at the time of diagnosis of stage IV pulmonary adenocarcinoma (PAC) treated with platinum-based chemotherapy (PBT). Objective. The authors investigated the effect of 1- to 4-month lag time to traditional Chinese medicine (TCM) treatment on the median and 1-year survival of PBT-PAC patients. Methods. The median lag time to treatment was 3 months. In the first 3 months, about 35% of the patients died, but thereafter the survival curve flattened off and the death of the next 35% to 40% of patients took 9 months. Leaving out patients with lag time up to 3 months therefore would be a reasonable choice. To be on the safe side, the effects of leaving out patients up to 4 months were investigated. The Kaplan–Meier survival curves were used. Results. The median and 1-year survival of the PBT-PAC patients was 5.0 months and 27%, respectively. Leaving out patients with 0-1 month follow-up, 0-2, 0-3, and 0-4 months follow-up changed the median and 1-year survival, respectively, to 5.5 months and 32%, 6.5 months and 36%, 9.0 months and 43%, and 10.0 months and 52%. The median survival of PBT + TCM in PAC patients was 22.6 months and 78%. Median lag time to TCM treatment was 3.0 months. With up to 4 months lag time to treatment due to combined patients’ and TCM doctor’s waiting time, the improved survival of PBT + TCM performance score 0-1 (fully ambulant) patients at the time of diagnosis still is significant (P < .01, hazard ratio = 0.51). Moreover, the survival of patients treated by TCM doctors with little or more months lag time to treatment was not different (P = .79). Conclusion. Increasing lag time to treatment up to 4 months improves the median and 1-year survival of PBT patients without TCM but is unlikely to explain the greatly improved prognosis of PBT + TCM treated patients with fully ambulant stage IV PAC. [ABSTRACT FROM PUBLISHER]

Background: Targeted therapy (TT), chemotherapy, and traditional Chinese medicine herbal treatment (TCM) can improve the prognosis of advanced pulmonary adenocarcinoma patients. Their independent prognostic value is unknown. Objective: To study whether TCM improves survival in stage IV pulmonary adenocarcinoma patients with platinum-based chemotherapy (PBT), or combined PBT and second-line TT. Methods: Retrospective analysis of 133 fully ambulant clinical outpatients treated with PBT alone or PBT with/without second-line TT, with/without TCM. Univariate (Kaplan—Meier) and multivariable (Cox model) survival analysis were performed, using disease-specific mortality as an endpoint. Results: Gender (P = .002), TT (P < .0001), and TCM (P < .0001) had univariate prognostic value but not age, radiotherapy, or TCM syndrome differentiation (P > .10). TCM herbal treatment (P < .0001) and TT (P = .03) had multivariable independent prognostic value. TCM-treated patients (n = 103, PBT+TT+TCM+ = 62; PBT+TT−TCM+ =41) had 88% 1-year overall survival rate with median survival time (MST) of 27 months, contrasting 27% 1-year overall survival and MST of 5.0 months for non-TCM-treated (n = 30) patients. Patients with chemotherapy/TT/TCM (PBT+TT+TCM+, n = 62), TCM without TT (PBT+TT−TCM+, n = 41), or chemotherapy only (PBT+TT−TCM−, n = 30), had 1-year survival rates of 94%, 78%, and 27% respectively; for these 3 groups, respectively, MST was not reached (MST of 30.9 months), 22.6, and 5.0 months (P < .0001). Conclusions: TCM herbal treatment may improve survival of stage IV pulmonary adenocarcinoma patients treated with chemotherapy without or with second-line TT. This warrants formal phase 1 and 2 trials and ultimately properly designed prospective clinical validation trials with adequate methodology developed for data collection. [ABSTRACT FROM PUBLISHER]

Objectives: To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1-4 endometrial endometrioid adenocarcinomas. Study design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2-5 markers positive). Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2-4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p=0.005). Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2-4 endometrial endometrioid adenocarcinomas. [ABSTRACT FROM AUTHOR]

Summary: The proliferation marker mitotic activity index is the strongest prognostic indicator in lymph node–negative breast cancer. The World Health Organization (WHO) 2003–defined procedure for determining WHO-mitotic activity index is often replaced by a quick scan mitotic impression. We evaluated the prognostic consequences of this practice in 433 T1-3N0M0 lymph node–negative invasive ductal type breast cancers with long-term follow-up (median, 112 months; range, 12-187 months). Twenty-seven percent of the studied cases developed distant metastases, and 25% died of disease. Agreement between WHO-mitotic activity index (0-5 = 1, 6-10 = 2, >10 = 3) and mitotic impression (1, 2, 3) categories was 66% (κ = 0.41), including 85% for category 1, 26% for category 2, and 52% for category 3. The WHO-mitotic activity index was a much stronger prognosticator than the mitotic impression, and the 10-year survival rates of the same categories (eg, mitotic activity index and mitotic impression category both 2) differed greatly. When grade was assessed by combining WHO-mitotic activity index or mitotic impression with the same values for tubular formation and nuclear atypia, grades disagreed in 18% of the cases. Deviation from the formal WHO-mitotic activity index assessment guidelines in breast cancer often results in erroneous prognosis estimations with therapeutic consequences and may explain why the prognostic value of proliferative activity in breast cancer is not always confirmed. [Copyright &y& Elsevier]

Recent studies based on epidemiological models published in this journal and elsewhere have demonstrated encouraging patterns suggesting that herbal treatment may improve prognosis in advanced colon and lung cancer patients. Various problems exist with data from nonrandomized studies of this type, but a strong signal of potential positive effect can be seen. The therapeutic mechanisms of traditional Chinese medicine in metastatic cancer are discussed against a hypothetical, dualistic antiproliferation model and immune-stimulation model of tumor progression and regression. Recommendations are made for a strategy to demonstrate more conclusively the efficacy of adjunct herbal treatment during cancer chemotherapy and for discussions with patients until such time as the efficacy trials are completed. [ABSTRACT FROM PUBLISHER]

Objective: The purpose of this study was to assess the value of the 2003 World Health Organization (WHO) and endometrial intraepithelial neoplasia (EIN) classifications, D-score, and molecular biomarkers in endometrial hyperplasia (EH) for cancer progression. Study Design: We conducted a review of 307 endometrial hyperplasias for WHO and EIN classifications and an analysis of biomarkers, D-score, and cancer progression-free survival. Results: The WHO, EIN, D-score, and many biomarkers were prognostic; 7.2% of the samples progressed to cancer. The WHO and EIN classifications correlated weakly with CK5/6 and p16. The D-score was strongest prognostically. When >1, it had the lowest false-negative progression rate of all features analyzed. COX2 negativity was the only other independent multivariate cancer progression predictor in endometrial hyperplasia, but only in cases with D-score <1. Eight of 13 cases (61%), with a combined D-score of <1 and negative COX2 progressed, which contrasted with 3 of 139 of all other cases (2.8%) (P < .0001; hazard ratio, 53.0). The biomarkers did not strengthen the prognostic value of the WHO or EIN classification. Conclusion: Combined D-score <1 and COX2 negativity strongly predict cancer progression in endometrial hyperplasias. [ABSTRACT FROM AUTHOR]

Objective: To analyze the prognostic value of molecular biomarkers in curettages of endometrioid endometrial cancer pathologic FIGO stages 1 and 2. Study Design: Population-based survival analysis in 258 patients of classical prognostic features and molecular biomarkers of cell cycle regulation, (anti)apoptosis, proliferation, squamous differentiation, and PTEN/Akt pathway. Results: With 74 months median follow-up (range, 1-209), 24 (9.3%) patients had metastases develop. Pathologic FIGO stage 2B (6% of all cases) and age > 68 years had independent multivariate prognostic value. Many molecular biomarkers were prognostic, particularly cell-cycle regulators p16, p21, p27, p53, p63, and the antiapoptosis marker survivin (which mostly stains mitoses). The strong prognostic value of a multivariate model with survivin, p21, and p53 overshadowed all other prognosticators in pathologic FIGO 1 and 2A. Conclusion: In pathologic FIGO stage 1 and 2A endometrioid endometrial cancer curettages, combined biomarkers survivin, p21, and p53 expression patterns are prognostically stronger than classical feature combinations. [Copyright &y& Elsevier]