Post-colonoscopy colorectal cancer in the Western Australian population: analysis of patient, histopathological and molecular characteristics.

Background: Post-colonoscopy colorectal cancer (PCCRC), defined as colorectal cancer (CRC) detected after a cancer-negative colonoscopy, represents a key quality indicator for CRC detection and prevention. While most PCCRC is attributed to missed lesions, few studies examine pathologic and molecular characteristics of PCCRC to assess for possible de novo cancer formation causing PCCRC.

Aim: The aim of this study was to identify cases of PCCRC where prior colonoscopy was adequate (A-PCCRC) versus inadequate (I-PCCRC) and compare both subtypes with spontaneous CRC (sCRC) in terms of patient factors, histopathology and molecular characteristics.

The Prognostic and Predictive Value of SOX2 Cell Densities in Patients Treated for Colorectal Cancer.

SOX2 (sex-determining region-Y homeobox-2) is a transcription factor essential for the maintenance of pluripotency and is also associated with stem-cell-like properties in preclinical cancer models. Our previous study on a cohort of stage III colon cancer patients demonstrated high SOX2 cell densities were associated with poor prognosis. However, most patients were treated with adjuvant chemotherapy so the prognostic value of SOX2 could not be assessed independently from its value as a predictive marker for non-response to chemotherapy.

Expression of PD-L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion.

Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer.

Universal molecular screening does not effectively detect Lynch syndrome in clinical practice.

Background: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC). Molecular testing using immunohistochemistry (IHC) for MMR proteins is a recommended screening tool to identify LS in incident CRC. This study assessed outcomes of population-based routine molecular screening for diagnosis of LS in a regional center.

The unfolded protein response is activated in Helicobacter-induced gastric carcinogenesis in a non-cell autonomous manner.

Mucous metaplasia (MM) is an aberrant secretory phenotype that arises during Helicobacter-induced gastric carcinogenesis. HSPA5, a key modulator of the unfolded protein response (UPR) activated by endoplasmic reticulum (ER) stress is overexpressed in gastric cancer (GC). We studied activation of the UPR in MM and GC in humans and mice.

Chasing the immortal strand: evidence for nature's way of protecting the breast genome.

Mutations arise during cell division at a predictable rate. Besides DNA repair mechanisms, the existence of cellular hierarchies that originate with a stem cell serve to reduce the number of divisions necessary for normal physiology. In a previous issue, Bussard and colleagues demonstrate that mammary stem cells have an additional remarkable trait; namely the ability to selectively retain a template DNA strand during self renewal.

Comprehensive mapping of p53 pathway alterations reveals an apparent role for both SNP309 and MDM2 amplification in sarcomagenesis.

Purpose: Reactivation of p53 tumor suppressor activity in diseases such as soft-tissue sarcoma is considered an attractive means of targeted therapy. By systematically assessing alterations affecting the p53 pathway, we aimed to (a) classify sarcoma subtypes, (b) define a potential role in malignancy, and (c) identify potential patient biomarkers in this heterogeneous disease.

Experimental Design: We have mapped mutational events in a panel of 192 benign or malignant bone and soft-tissue sarcomas.

Thyroid pathology in four patients with Cowden's disease.

Cowden's disease (multiple hamartoma syndrome) is a rare genodermatosis, which carries an increased risk of malignancy, especially breast and thyroid carcinoma. Thyroid disease is the most common internal manifestation of the syndrome, but the histological features in benign cases have hitherto been relatively poorly described. Thyroidectomy specimens from four patients with Cowden's disease have been reported in our laboratory in recent years.