Changing Pathology with Changing Drugs: Tumors of the Gastrointestinal Tract

Abstract

Gastrointestinal cancer treatment is being based more and more on pathology that yields integrated information leading to targeted therapy, i.e. morphological identification of the histological type of the tumor and its context, staging of the tumor, and identification of various targets. This provides a realistic appraisal of the tumor and allows surgeons and oncologists to choose the best treatment from an increased range of drug options. An accurate diagnosis remains the major determinant of treatment, but new drugs and new insights into molecular pathways acting in carcinogenesis enhance molecular diagnosis in cancer. In most adenocarcinomas, therapy is only organ orientated and staging dependent, and not patient targeted. Currently, the identification and validation of new targets as well as molecular classification of the tumors are inducing the incorporation of new tests into the daily practice of surgical pathology. These new tests require appropriate tissue preservation and selection of the tissue to be analyzed and harmonized to morphological criteria. In colorectal adenocarcinoma, which is the second most common malignant tumor in both genders, the biomarkers that are relevant at the present time are the genetic instability status of the tumor, the KRAS mutation status as a negative predictive marker for the overall rate of response to anti-EGFR treatment in patients with metastatic cancer, and BRAF mutation as an unfavorable prognostic marker. In gastric adenocarcinoma, HER2 overexpression is correlated with poor outcomes and more aggressive disease in a subset of cases with clinical response to trastuzumab. Met mutations have also been evidenced. Hepatocellular carcinoma is a highly chemoresistant tumor with several genetic alterations. Pancreatic adenocarcinoma is a leading cause of cancer death with frequent KRAS mutations. No biomarker has been clearly identified in either of these tumors. Gastrointestinal stromal tumors that constitute less than 3% of all gastrointestinal malignancies have been individualized since 1988. They express the KIT protein, a membrane receptor, and respond to imatinib which is a tyrosine kinase receptor inhibitor, depending on the mutational status of the tumor.

Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage

“…Approximately 60% of patients who undergo curative resection experience local recurrence or distant metastases [1]. The primary treatment of CRC is surgical resection of the primary tumor and possibly the regional lymph nodes; this may be combined with chemotherapy, depending on the depth of tumor penetration and the disease stage [2]. The development and progression of a tumor is controlled by oncogenes and tumor suppressor genes.…”

Unusual Spreading of Colon Adenocarcinoma into the Right Hip Area: A Case Report

“…We present the very unusual case of extraluminal colon carcinoma spreading from the abdomen through the right hip area "per continuitatem". To the best of our knowledge, we didn't find similar case published in the literature, where extraluminal colonic adenocarcinoma directly invaded into the hip [5][6][7][8][9][10][11][12][13]. Our patient did not have any sign of distant metastasis in the same time when local tumor was more than 20 cm.…”

The Use of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) in Cytopathology Diagnosis

“…Many assays have become clinically available in identifying genetic alterations that serve as prognostic markers and therapeutic targets. EGFR expression in head and neck cancers, non-small cell lung carcinomas, colon cancers, and recently in pancreatic cancers [73][74][75][76][77][78][79][80][81][82]; microsatellite instability tests in colon cancer serve as prognostic marker, therapeutic predictive marker and screening test for Lynch syndrome [83][84][85][86][87][88] are among the most studied areas. Immunodetection of molecular markers on cytology specimen, especially in cancer staging for metastatic disease will be playing a major role as a guide for moleculartargeted therapy.…”