Oligonucleotide-Directed Microarray Gene Profiling of Pancreatic Adenocarcinoma

Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (pless than 0.001) for both receptors (ER: 0.34 and PR: 0.54). Concordance was shown in 61 (82%) cases and discordance in 13 (18%) of the 74 tumours tested. Further stratification by MP/BP identified 49 (66.2%) Luminal A, 21 (28.4%) Luminal B and 4 (5.4%) Basal-like tumours. Neither IHC nor TargetPrint could substitute BP subtyping, which measures the functional integrity of ER and can identify patients with false-positive tumours who are resistant to hormone therapy. These findings support the implementation of a pathology-supported genetic testing approach combining IHC and microarray gene profiling for definitive prognostic and predictive treatment decision-making in patients with early stage breast cancer. Significance: Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results. Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping. Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status. Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.

Download Full-text

198. Identification of Novel TNF-a Regulated Extracellular Matrix and Cell-matrix Adhesion Genes in Intervertebral Disc Cells: A Microarray Gene Profiling of Human Nucleus Pulposus Cells

The Spine Journal ◽

10.1016/j.spinee.2008.06.237 ◽

2008 ◽

Vol 8 (5) ◽

pp. 99S-100S ◽

Cited By ~ 1

Author(s):

Nam Vo ◽

Christopher Seidel ◽

Paulo Coelho ◽

Gwendolyn Sowa ◽

Rebecca Studer ◽

...

Keyword(s):

Extracellular Matrix ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Gene Profiling ◽

Nucleus Pulposus Cells ◽

Matrix Adhesion ◽

Cell Matrix ◽

Disc Cells ◽

Microarray Gene ◽

Cell Matrix Adhesion

Download Full-text

Microarray gene profiling of laser-captured cells: A new tool to study atherosclerosis in mice

Atherosclerosis ◽

10.1016/j.atherosclerosis.2007.12.056 ◽

2008 ◽

Vol 200 (2) ◽

pp. 257-263 ◽

Cited By ~ 11

Author(s):

Antoni Paul ◽

Vijay Yechoor ◽

Rajiv Raja ◽

Lan Li ◽

Lawrence Chan

Keyword(s):

Gene Profiling ◽

Microarray Gene

Download Full-text

The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by FAK Inhibitor Y15 and Combination of Y15 and Temozolomide

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/18715206113139990141 ◽

2014 ◽

Vol 14 (1) ◽

pp. 9-17 ◽

Cited By ~ 16

Author(s):

Grace Huang ◽

Baotran Ho ◽

Jeffrey Conroy ◽

Song Liu ◽

Hu Qiang ◽

...

Keyword(s):

Cancer Cells ◽

Gene Profiling ◽

Microarray Gene ◽

Profiling Analysis

Download Full-text

Identifiable Mutations in Pancreatic Adenocarcinoma in the Veteran Population: Molecular Testing Guidelines by NCCN 2020

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab191.307 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S144-S144

Author(s):

J M Petersen ◽

D Jhala

Keyword(s):

Pancreatic Adenocarcinoma ◽

Medical Center ◽

Locally Advanced ◽

Standard Of Care ◽

Gene Profiling ◽

Molecular Testing ◽

Nccn Guidelines ◽

Cdkn2a Mutation ◽

Frequent Mutations ◽

Locally Advanced Pancreatic Adenocarcinoma

Abstract Introduction/Objective In 2019 and 2020, the National Comprehensive Cancer Network (NCCN) advanced a recommendation that all patients with metastatic, recurrent, or locally advanced pancreatic adenocarcinoma should undergo tumor gene profiling (TGP). Prior to these recommendations, TGP in targeted patients have demonstrated a high frequency of KRAS (>90%), TP53 (60-70%), CDKN2A (>50%), SMAD4, TGF- βR1, and TGF- βR2 mutations or alterations. Even less frequent mutations such as the homologous recombination repair (HRR) genes impact treatment by predicting tumor response to platinum-based therapies. However, the literature is sparse for the frequency of these mutations in patients with pancreatic adenocarcinoma undergoing generalized testing as part of the standard of care per NCCN guidance, particularly for veterans. Methods/Case Report For a quality assurance study, a retrospective review was performed to identify patients with pancreatic adenocarcinoma at a tertiary medical center serving veterans from January 2019 to February 2021 with TGP performed as part of their care. All of the TGP had been sent to Foundation Medicine (Cambridge MA), and the identifiable tumor mutations from the test reports were recorded to document the frequency of KRAS, TP53, CDKN2A, SMAD4, TGF- βR1, TGF- βR2 and HRR mutations or alterations. Results (if a Case Study enter NA) There were a total of 11 patients with pancreatic adenocarcinoma who had a tumor specimen for TGP during the study period. All 11 patient tumors had KRAS mutation. 10 out of 11 had a mutation or alteration in TP53. 8 of 11 patients had a CDKN2A mutation or alteration. 7 of 11 patients had a mutation or alteration of SMAD4 though none had TGF- βR1 or TGF- βR2. 2 of 11 patients had HRR mutations (1 with FANCA and 1 with ATM). Conclusion Tumor mutations on generalized gene profiling per NCCN guidelines continue to identify important mutations in pancreatic adenocarcinoma for veteran patients.

Download Full-text