pCR In Surgical Specimen Research Articles

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.

Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration.Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS).Results: Median age at diagnosis was 74 (range, 42–100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045).Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.

Can a pathological complete response of breast cancer after neoadjuvant chemotherapy be diagnosed by minimal invasive biopsy?

BackgroundThis study aimed to explore the ability of a minimal invasive biopsy to diagnose a pathological complete response (pCR = ypT0) in the breast. MethodsUltrasound-guided, vacuum-assisted, minimal invasive biopsy (VAB) was performed in 50 patients after neoadjuvant chemotherapy and before breast surgery. Negative predictive values (NPV) and false negative rates (FNR) to predict a pCR in surgical specimen were the main outcome measures. To assess the possible sampling error, the representativeness of the sample was evaluated by the biopsy performing physician (subjectively based on the visibility in ultrasound), by radiography of the biopsy specimen, and by the pathologist (based on histopathology). ResultsThe cohort (n = 50) consisted of 15 (30%) triple negative breast cancers, 13 (26%) human epidermal growth factor receptor 2 (HER2) positive and 22 (44%) hormone receptor positive/HER2 negative cancers. ypT0 was diagnosed in 23 (46%) cases. In the overall cohort (n = 50), VAB yielded an NPV of 76.7% and an FNR of 25.9%. Given a representative VAB sample, according to the histopathological evaluation (n = 38), the NPV was 94.4% (95% CI 87.1–100.0) and the FNR 4.8% (95% CI 0.0–11.6). Non-representative VABs were mainly due to bad visibility of the target lesion in ultrasound. ConclusionA VAB can accurately diagnose a pCR, given a histopathologically representative sample.

Abstract P5-02-01: Diagnosis of pathological complete response by vacuum-assisted minimal invasive biopsy after neoadjuvant chemotherapy in breast cancer - Results from a prospective pilot study

Abstract Purpose: To explore the ability of vacuum-assisted-biopsy (VAB) to diagnose pathological complete response (pCR) or residual tumor in breast cancer patients after neoadjuvant chemotherapy (NACT). Patients and methods: 50 patients (22 with clinical / imaging complete response 28 with clinical / imaging residual tumor) were included in this review-board approved prospective pilot study between 08/14 and 02/15. Vacuum-assisted-biopsy (VAB) was performed after NACT and before surgery. Negative predictive values (NPV) and false-negative-rates (FNR) to predict a pCR in surgical specimen (=diagnose pCR through VAB) were the main outcome measures. Results: The cohort (n=50) consisted of 15 (30%) triple negative (TNBC), 13 (26%) HER2 positive (HER2+) and 22 (44%) hormone receptor positive / HER2 negative (HR+/HER2-) cancers. pCR in surgical specimen was diagnosed in 23 (46%) cases of the whole cohort. The NPV of the VAB diagnosis of pCR was 94.4% (95% CI: [0.84; 1.00]). The FNR was 3.7% (95% CI: [0; 0.12]) and specificity 73.9% (95% CI: [0.54; 0.94]). Taking only those biopsies into account that pathology confirmed to be representative of the (former) tumor region, improved the outcome of VAB to a specificity of 100% while the NPV (94.4% (95% CI: [0.84; 1.00]) and the FNR (4.8% (95% CI: [0.00; 0.15]) stayed the same. Conclusion: Overall accuracy of VAB diagnosis of pCR questions the necessity of surgical intervention to diagnose a pCR. A confirmative, multi-center, intra-individually-controlled clinical trial including patients with clinical complete, near complete or partial response to NACT to validate the above mentioned results is warranted. Citation Format: Hennigs A, Heil J. Diagnosis of pathological complete response by vacuum-assisted minimal invasive biopsy after neoadjuvant chemotherapy in breast cancer - Results from a prospective pilot study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-02-01.

Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques.

Background:Neoadjuvant chemotherapy (NACT) is widely used as an efficient breast cancer treatment. Ideally, a pathological complete response (pCR) can be achieved. Up to date, there is no reliable way of predicting a pCR. For the first time, we explore the ability of minimal invasive biopsy (MIB) techniques to diagnose pCR in patients with clinical complete response (cCR) to NACT in this study. This question is of high clinical relevance because a reliable pCR prediction could have direct implications for clinical practice.Methods:In all, 164 patients were included in this review-board approved, multicenter pooled analysis of prospectively assembled data. Core-cut (CC)-MIB or vacuum-assisted (VAB)-MIB were performed after NACT and before surgery. Negative predictive values (NPV) and false-negative rates (FNR) to predict a pCR in surgical specimen (diagnose pCR through MIB) were the main outcome measures.Results:Pathological complete response in surgical specimen was diagnosed in 93 (56.7%) cases of the whole cohort. The NPV of the MIB diagnosis of pCR was 71.3% (95% CI: (63.3% 79.3%)). The FNR was 49.3% (95% CI: (40.4% 58.2%)). Existence of a clip marker tended to improve the NPV (odds ratio 1.98; 95% CI: (0.81; 4.85)). None of the mammographically guided VABs (n=16) was false-negative (FNR 0%, NPV 100%).Conclusions:Overall accuracy of MIB diagnosis of pCR was insufficient to suggest changing clinical practice. However, subgroup analyses (mammographically guided VABs) suggest a potential capacity of MIB techniques to precisely diagnose pCR after NACT. Representativity of MIB could be a crucial factor to be focused on in further analyses.