Overview
Calretinin is a calcium (Ca²⁺)-binding intracellular protein belonging to the calmodulin superfamily and is also known as calbindin 2. It is encoded by the CALB2 gene and plays an important role in intracellular calcium signaling, message targeting, cell cycle arrest, and apoptosis. It is expressed in both normal and pathological tissues, including mesothelium, mast cells, certain neural cells, and adipose tissue.
Clinically, it serves as a valuable diagnostic and prognostic marker, particularly in malignant mesothelioma. It is widely used to differentiate malignant pleural mesothelioma from lung adenocarcinoma, where this expression is typically absent. Antibodies against calretinin are used in immunohistochemistry (IHC) to identify mesothelial lineage and specific tumor types. Additionally, it is an important ancillary marker in the diagnosis of Hirschsprung’s disease, as it reliably identifies the presence or absence of ganglion cells. Detection methods include immunohistochemistry on formalin-fixed paraffin-embedded tissue and ELISA-based serum testing. Calretinin
Symptoms
It itself does not produce clinical symptoms, as it is a diagnostic biomarker rather than a disease entity. However, testing is performed in clinical conditions where underlying pathology produces symptoms. In malignant mesothelioma, patients may present with chest pain, pleural effusion, or respiratory distress. In Hirschsprung’s disease, symptoms include chronic constipation, abdominal distension, and intestinal obstruction due to the absence of enteric ganglion cells. Neurological or tumor-related symptoms may be present depending on the tissue involved and the associated disease process.
Causes
Altered calretinin expression is associated with several pathological conditions. Strong calretinin positivity is seen in malignant mesothelioma, particularly in epithelioid and biphasic subtypes, with lower expression in sarcomatoid mesothelioma. It is also expressed in ovarian sex cord-stromal tumors, deep fibromatosis, schwannomas (patchy expression), and certain neural-derived tumors.
In Hirschsprung’s disease, the absence of calretinin staining indicates aganglionosis, while positive staining confirms the presence of ganglion cells regardless of biopsy depth, site, or nerve hypertrophy. It is also useful in diagnosing adrenal cortical lesions, mesonephric carcinoma, female adnexal tumor of probable Wolffian origin (FATWO), STK11 adnexal tumors, and tumors of mesothelial lineage. Most adenocarcinomas show negative calretinin staining, making it a useful differential marker.
Risk Factors
Risk factors for conditions associated with calretinin positivity depend on the underlying disease rather than the marker itself. Asbestos exposure is a major risk factor for malignant mesothelioma. Genetic and developmental factors increase the risk of Hirschsprung’s disease. Certain tumor types, including sex cord-stromal tumors and mesothelial neoplasms, inherently show higher calretinin expression. Improper tissue sampling, fixation, or handling may affect staining patterns and interpretation, emphasizing the importance of standardized laboratory procedures.
Prevention
There is no direct prevention related to calretinin expression, as it is a diagnostic marker rather than a causative agent. However, prevention of associated diseases includes minimizing asbestos exposure to reduce the risk of mesothelioma and early screening in high-risk populations. Accurate diagnosis relies on proper tissue collection, fixation, and immunohistochemical processing. In Hirschsprung’s disease, early diagnosis using calretinin staining allows timely surgical intervention and prevention of complications. Regular quality control in laboratories and appropriate use of calretinin in diagnostic panels help ensure accurate disease identification and optimal patient management.
