Standardization in immunohistology

The rapid acceptance of immunohistology as an invaluable adjunct to morphologic diagnosis has been possible because of the development of new and more sensitive antibodies and detection systems that allow its application to formalin-fixed, paraffin-embedded tissue (FFPT). More importantly, antigen-retrieval techniques have resulted in some degree of consistency allowing immunohistology to be used reliably as a diagnostic tool. The advent of prognostic and predictive biomarkers, and the desire for individualized therapy has resulted in mounting pressure to employ the immunohistological assay in a quantitative manner. While it was not a major issue when the technique was employed in a qualitative manner, the numerous variables in the preanalytical and analytical phases of the test procedure that influence the immunoexpression of proteins in FFPT become critical to standardization. Tissue fixation is pivotal to antigen preservation but exposure to fixative prior to accessioning by the laboratory is not controlled. Antigen retrieval, crucial in the analytical phase, continues to be employed in an empirical manner with the actual mechanism of action remaining elusive. There is great variation in reagents, methodology, and duration of tissue processing and immunostaining procedure, and the detection systems employed are not standardized between laboratories. While many of these variables are offset by the application of antigen retrieval, which enables the detection of a wide range of antigens in FFPT, the method itself is not standardized. This myriad of variables makes it inappropriate to provide meaningful comparisons of results obtained in different laboratories and even in the same laboratory, as in current practice, each specimen experiences different preanalytical variables. Furthermore, variables in interpretation exist and cutoff thresholds for positivity differ. Failure to recognize false-positive and false-negative stains leads to further errors of quantitative measurement. Many of the problems relating to the technology and interpretation of immunostaining originate from failure to recognize that this procedure is different from other histological stains and involves many more steps that cannot be monitored until the end result is attained. While several remedial measures can be suggested to address some of these problems, accurate and reproducible quantitative assessment of immunostains presently remains elusive as important variables that impact on antigen preservation in the paraffin-embedded biopsy cannot be standardized

Epidemiology

Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide. In some countries of high incidence, HCC is the leading form of cancer; and overall, it rates as the seventh most common malignancy in males and the ninth most in females. Cancer statistics from many of the countries with a high incidence of HCC are incomplete; as such, much of the available data may represent underestimates. At least one million new cases of HCC occur annually and mortality from the disease remains high despite treatment, with recent results showing 1-year, 3-year, and 5-year overall survival rates of 66.1%, 39.7%, and 32.5%, respectively; and 93.5%, 70.1%, and 59.1% for early-stage patients, respectively. Even in countries where the incidence is low, the median survival time after resection is 24.8 months compared to 5.8 months in symptomatically treated patients

Pathology

Hepacocellular carcinoma (HCC) is a malignant tumor derived from heparocytes. It is the most frequent primary tumor of the liver; in a series of 6391 cases of primary liver cancer, 4317 (67.5%) were found to be HCCs. The most common etiological factors related to HCC are hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, dietary aflatoxin ingestion, and chronic alcohol abuse

Australian consensus statement for best practice ROS1 testing in advanced non-small cell lung cancer

Lung cancer is the most commonly diagnosed malignancy and the leading cause of death from cancer globally. Diagnosis of advanced non-small cell lung cancer (NSCLC) is associated with 5-year relative survival of 3.2%. ROS proto-oncogene 1 (ROS1) is an oncogenic driver of NSCLC occurring in up to 2% of cases and commonly associated with younger age and a history of never or light smoking. Results of an early trial with the tyrosine kinase inhibitor (TKI) crizotinib that inhibits tumours that harbour ROS1 rearrangements have shown an objective response rate (ORR) of 72% (95% CI 58–83%), median progression free survival (PFS) of 19.3 months (95% CI 15.2–39.1 months) and median overall survival (OS) of 51.4 months (95% CI 29.3 months to not reached). Therefore, with the availability of highly effective ROS1-targeted TKI therapy, upfront molecular testing for ROS1 status alongside EGFR and ALK testing is recommended for all patients with NSCLC. We review the tissue requirements for ROS1 testing by immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) and we present a testing algorithm for advanced NSCLC and consider how the future of pathology testing for ROS1 may evolve.</p

National Working Group Meeting on ALK diagnostics in lung cancer

The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors

Epidemiology and carcinogenesis of hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide but the magnitude of this tumor is reflected by the occurrence of at least 1 million new cases annually and the uniformly dismal outlook with median survivals of <25 months after resection and <6 months with symptomatic treatment. The strikingly uneven distribution of this tumor parallels the prevalence of hepatitis B infection with rising incidence in western countries attributed to hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major preneoplastic conditions in the majority of HCCs and may be related to other etiologic agents such as environmental chemical carcinogens including nitrites, hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins such as anatoxins produced by fungi that cause spoilage of grain and food in the tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease, α-1-antitrypsin deficiency, and the inborn errors of metabolism including hereditary tyrosinemia and hepatic porphyria, are known to be associated with HCC. Numerous genetic alterations and the modulation of DNA methylation are recognized in HCC and it is likely that these genetic and epigenetic changes combine with factors involved in chronic hepatocyte destruction and regeneration to result in neoplastic growth and multiple molecular pathways may be involved in the production of subsets of hepatocellular tumors