THE ROLE OF IMMUNOHISTOCHEMICAL MARKERS IN PREDICTING RECURRENCE OR DEATH IN PATIENTS WITH MEDULAR THYROID CANCER

Introduction. Medullary thyroid cancer (MTC) belongs to a class of rare neuroendocrine aggressive tumors and arises from parafollicular cells (C-cells). An important modern problem is the development of ways to predict the recurrence of this disease. The aim of the study is to determine the role of immunohistochemical tumor markers of medullary thyroid cancer in predicting recurrence or death. Materials and methods. The analysis of the prospective study included 22 patients with MTC, 5 of whom have developed a recurrence and 4 have died at the end of the 10-year (120 months) follow-up period. Immunohistochemical examinations were performed using monoclonal antibodies of tumor markers calcitonin, chromogranin A, vimentin and Ki-67. Results. The discrepancy between the data of histological and immunohistochemical examinations in MTC is 12.0%, which indicates the hyperdiagnosis of this nosology and argues the importance of performing immunohistochemical examinations to verify the diagnosis. Patients who had a recurrence of MTC had significantly (p <0.05) lower levels of calcitonin expression (5.00 [5.00; 5.00] points) compared with patients who did not relapse, where this figure was 6.00 [6.00; 7.00] points. In patients with MTC, an increase in calcitonin expression was significantly associated with an increase in chromogranin A expression (r = + 0.49, p = 0.02); a similar relationship was found for the proportions of immunopositive cells of these tumor markers: r = + 0.68, p = 0.001. At the same time, it was found that the increase in the level of calcitonin expression was apparently combined with the decrease in the level of Ki-67 expression (r = -0.52, p = 0.02). It was also found that the increase in the level of vimentin expression is combined with an increase in the expression (r = + 0.64, p = 0.001) and the proportion of immunopositive cells of chromogranin A (r = + 0.45, p = 0.038). Conclusions. Low levels of calcitonin expression are prognostically unfavorable markers for the recurrence of MTC. Specific tumor markers are important in the treatment process and for the dynamic monitoring of patients with MTC.

Performance Evaluation of the KRYPTOR Compact PLUS Analyzer-Based B.R.A.H.M.S. CgA Ⅱ KRYPTOR Assay for Chromogranin A Measurement

Numerous immunoassays have been developed to measure the levels of chromogranin A (CgA), a useful biomarker for diagnosing and monitoring generally heterogeneous neuroendocrine tumors (NETs). Here, we evaluated the imprecision and linearity of three such assays: KRYPTOR (ThermoFisher Scientific), NEOLISA (EuroDiagnostica), and CgA-RIA (CisBio), using 123 samples for each assay. The correlation coefficients between the assays were 0.932 (CgA-RIA versus NEOLISA), 0.956 (KRYPTOR versus CgA-RIA), and 0.873 (NEOLISA versus KRYPTOR). KRYPTOR showed good precision, with percent coefficients of variation less than 5% for low and high concentration quality controls. Linearity was maintained over a wide concentration range. Comparison of CgA levels from three disease entities (NETs, non-NET pancreatic tumors, and prostate cancer) and healthy controls showed that patients with NETs had significantly higher CgA levels (n = 57, mean: 1.82 ± 0.43 log ng/mL) than healthy individuals (n = 20, mean: 1.51 ± 0.23 log ng/mL; p = 0.018). No other significant differences between groups were observed. All three immunoassays showed strong correlations in measured CgA levels. Because KRYPTOR operation uses a fully automated random-access system and requires shorter incubation times and smaller sample volumes, the KRYPTOR assay may improve laboratory workflow while maintaining satisfactory analytical performance.

The Expression of Chromogranin A, Syanptophysin and Ki67 in Detecting Neuroendocrine Neoplasma at High Grade Colorectal Adenocarcinoma

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases.

The Prognostic and Predictive Role of Chromogranin A in Gastroenteropancreatic Neuroendocrine Tumors – A Single-Center Experience

Chromogranin A (CgA) is a non-specific biomarker excreted by neuroendocrine tumor (NET) cells. Elevation of circulating CgA level can be detected in gastroenteropancreatic (GEP)-NET patients and has been shown to correlate with tumor burden. The prognostic and predictive roles of CgA level and the change of CgA level are controversial. In this study, we retrospectively analyzed 102 grade 1/2 GEP-NET patients with available baseline or serial follow-up CgA levels from the National Cheng Kung University Hospital to evaluate the association between circulating CgA level and the tumor extent, overall survival (OS), and tumor response prediction. The baseline characteristics, baseline CgA level, and change of CgA level during follow-up and their association was analyzed. Sixty cases had baseline CgA levels available prior to any treatment and ninety-four cases had serial follow-up CgA levels available during treatment or surveillance. Baseline CgA levels were associated with stage and sex. Higher baseline CgA levels were associated with worse OS after adjusting for sex, stage, grade, primary site, and functionality (hazard ratio=13.52, 95% confidence interval (CI), 1.06-172.47, P=0.045). The cross-sectional analysis for the change of CgA level during follow-up showed that a ≥ 40% increase of CgA meant a higher probability of developing tumor progression or recurrence than those with a &lt; 40% increase of CgA level (odds ratio=5.04, 95% CI, 1.31-19.4, P=0.019) after adjusting for sex, age, grade, stage, and functionality. Our study results suggest that CgA may be a predictive marker for tumor burden, OS, and tumor progression in GEP-NET patients.