Association Between RAS/BRAF Mutations and Complete Response Following Total Neoadjuvant Therapy in Patients with Rectal Cancer: A Prospective Multicentered Study.

Background: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status.

Methods: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023.

Young-onset colorectal cancer is associated with a personal history of type 2 diabetes.

Background: Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young-onset colorectal cancer (YOCRC).

Methods: The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55.

Identification of microRNA Biomarkers of Response to Neoadjuvant Chemoradiotherapy in Esophageal Adenocarcinoma Using Next Generation Sequencing.

Background: Clinical trials report improved overall survival following neoadjuvant chemoradiotherapy in patients undergoing surgery for esophageal adenocarcinoma, with a 10-15% survival improvement. MicroRNAs (miRNAs) are small noncoding RNAs that are known to direct the behavior of cancers, including response to treatment. We investigated the ability of miRNAs to predict outcomes after neoadjuvant chemoradiotherapy.

Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.

Aim: In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC.

Androgen Receptor and Androgen-Responsive Gene FKBP5 Are Independent Prognostic Indicators for Esophageal Adenocarcinoma.

Background: Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.

Aims: To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma.

Methods: Expression of AR and FKBP5 was determined by immunohistochemistry.

Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer.

Background: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.

Methods: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort.

PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer.

Purpose: PIK3CA and PTEN mutations are prevalent in colorectal cancer and potential markers of response to mitogen-activated protein/extracellular signal-regulated kinase inhibitors and anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, and prognosis remain controversial.

Experimental Design: A total of 1,093 stage I-IV colorectal cancers were screened for PIK3CA (exons 9 and 20), KRAS (codons 12-13), BRAF (codon 600) mutations, and microsatellite instability (MSI).

SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer.

Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis.

Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival.

Background: HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown.

Materials And Methods: Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH).

Feasibility study of sentinel lymph node biopsy in esophageal cancer with conservative lymphadenectomy.

Introduction: Lymphoscintigraphy and sentinel node mapping is established in breast cancer and melanoma but not in esophageal cancer, even though many centers have shown that occult tumor deposits in lymph nodes influence prognosis. We report our initial experience with lymphoscintigraphy and sentinel lymph node biopsy in patients undergoing resection for esophageal cancer.

Methods: Sixteen of 17 consecutive patients underwent resection for invasive esophageal cancer along with sentinel lymph node retrieval (resection rate, 94%).

Isolated tumor cells in esophageal cancer: implications for the surgeon and the pathologist.

Introduction: Studies suggest that up to 56% of node-negative patients have tumor deposits in their lymph nodes that are missed by routine pathologic examination. However, few studies differentiate between isolated tumor cells and micrometastases using reproducible criteria, and their prognostic significance has not been established.

Methods: We identified 119 patients who had undergone surgical resection for esophageal cancer between 1997 and 2007, and who were classified as node-negative.

Analysis of families with Lynch syndrome complicated by advanced serrated neoplasia: the importance of pathology review and pedigree analysis.

The identification of Lynch syndrome has been greatly assisted by the advent of tumour immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and by the recognition of the role of acquired somatic BRAF mutation in sporadic MMR-deficient colorectal cancer (CRC). However, somatic BRAF mutation may also be present in the tumours in families with a predisposition to develop serrated polyps in the colorectum. In a subgroup of affected members in these families, CRCs emerge which demonstrate clear evidence of MMR deficiency with absent MLH1 staining and high-level microsatellite instability (MSI).

Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma.

Background: Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC.

Improving the accuracy of TNM staging in esophageal cancer: a pathological review of resected specimens.

Background: Controversy exists over the Sixth Edition of the International Union Against Cancer (UICC) TNM staging system for esophageal cancer. Inclusion of additional information such as the number of metastatic lymph nodes and extracapsular lymph node invasion may improve the current staging system and lead to optimization of patient treatment.

Methods: All patients in Adelaide who underwent resection for esophageal cancer between 1997 and 2007 were identified from a prospective database.

Methylation of TIMP3 in esophageal squamous cell carcinoma.

Aim: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China.

Methods: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2'-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR.

Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study.

Background & Aims: The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H).

Methods: Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI.

Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation.

Purpose: Most colorectal cancers that have high levels of microsatellite instability (MSI-H) show loss of immunohistochemical expression of proteins that participate in the DNA mismatch repair process, most often involving MLH1 and MSH2. Less commonly, a third DNA mismatch repair protein, MSH6, may also be lost as the primary event. Rarely, tumors with MSI-H show normal expression of these three proteins.