Elsevier

Human Pathology

Volume 41, Issue 5, May 2010, Pages 745-750
Human Pathology

Original contribution
IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and malignant cells: the expression profiles of IMP3/L523S in effusion cytology

https://doi.org/10.1016/j.humpath.2009.04.030Get rights and content

Summary

Differentiating reactive mesothelial cells from metastatic carcinoma and malignant mesothelioma is critical in effusion cytology. Numerous immunohistochemical/cytochemical reports use various antibodies in effusion samples, and most antibodies differentiate metastatic adenocarcinoma from malignant mesothelioma, but no antibodies help distinguish malignant mesothelioma from reactive mesothelial cells. A mouse monoclonal antibody (IMP3/L523S) against KOC is a 580-amino acid oncofetal RNA-binding protein containing 4 K homology domains. IMP3/L523S has been identified in several human malignant tumors. The immunocytochemical staining profile of IMP3 was determined in 95% alcohol-fixed cytologic effusion specimens. A total of 229 cases of pleural and peritoneal effusion cytospecimens were evaluated for the study, including 39 benign effusions with reactive mesothelial cells and 190 metastatic malignant effusions. IMP3 immunoreactivity was observed in 2 (5.1%) of 39 cases of reactive mesothelial cells, 138 (72.6%) of 190 cases of malignant effusion, 4 (36.4%) of 11 cases of malignant mesothelioma, 106 (75.7%) of 140 cases of metastatic adenocarcinoma, and 8 (100%) of 8 cases of squamous cell carcinoma. The overall specificity for the diagnosis of malignancy was 94.9%, whereas the sensitivity was 72.6%. In the peritoneal effusions, the sensitivity for the diagnosis of metastatic adenocarcinoma to distinguish reactive mesothelial cells was 92.3%. In conclusion, IMP3 staining is present in many carcinomas and is not a useful marker for distinguishing between carcinomas arising in different organs. However, the IMP3 antibody is a highly specific marker for malignant lesions, and thus, IMP3 staining is useful for distinguishing neoplastic cells from reactive mesothelial cells in effusion samples.

Introduction

The appearance of neoplastic cells in effusions is an important factor for determining the prognosis and treatment, and in effusion cytology, differentiating reactive mesothelial cells (RMs) from metastatic carcinoma and malignant mesothelioma (MM) is critical. There are numerous immunohistochemical/cytochemical reports using various antibodies in effusion samples, and these antibodies are very useful and often used for routine examinations. Most of these antibodies are useful for differentiating metastatic adenocarcinoma (AC) from MM; however, there are no antibodies that help distinguish MM from RMs [1]. Recently, the anti-L523S antibody has been reported to be a useful marker for the detection of neoplastic cells in serous effusions [2].

The K homology (KH) domain, pre–mRNA-binding heterogeneous nuclear ribonucleoprotein K protein, is found in a number of RNA-binding proteins, and KH domain containing proteins are involved in the regulation of RNA stability [3], [4]. In large-scale screening for differentially expressed genes in pancreatic cancer, a gene encoding a novel protein with 4 KH domains was identified, and the new protein was named KOC (KH domain containing protein overexpressed in cancer) [5]. KOC is a 580-amino acid oncofetal RNA-binding protein containing 4 KH domains [5], [6]. This protein regulates insulin-like growth factor II transcripts during embryogenesis and is later reexpressed in a proportion of neoplastic cells from various tumor types, including pancreatic and lung [2], [5], [7], [8]. A mouse monoclonal antibody IMP3/L523S (insulin-like growth factor II mRNA-binding protein 3) was raised against KOC.

The expression profiles of IMP3/L523S in effusion samples have been reported [2], [9]. However, the number of cases was insufficient, and the samples were paraffin-embedded effusion cell blocks for immunohistochemistry. This study determined the immunocytochemical staining profile of IMP3 in 95% alcohol-fixed cytologic effusion specimens.

Section snippets

Case selection

A cohort of patients with malignant effusions was identified. All malignant cases were confirmed by surgical biopsy or resection at the primary site. MM diagnoses were based on morphological criteria, supporting immunohistochemical staining, and the clinical findings. In the effusion cytodiagnosis of MM, all the MM cases were finally diagnosed by either a surgical biopsy or a resected specimen, supported by the findings of immunocytochemical staining, such as mesothelium-associated markers,

Results

The immunocytochemical results are listed in Table 1. IMP3 expression was demonstrated by distinct cytoplasmic staining. A total of 229 cases were identified, including 39 specimens from RMs and 190 specimens from malignant cases. IMP3 immunoreactivity was observed in 2 (5.1%) of 39 specimens from RMs, 138 (72.6%) of 190 specimens from malignant effusion, 4 (36.4%) of 11 specimens from MM, 106 (75.7%) of 140 specimens from AC, and 8 (100%) of 8 specimens from SCC. The overall specificity for

Discussion

In effusion cytology, differentiating RMs from metastatic carcinoma and MM is critical. The difficulty is compounded when neoplastic cells exhibit only slight atypia and when RMs demonstrate marked atypia. Numerous immunohistochemical/cytochemical reports have used various antibodies in effusion samples, and these antibodies are very useful and often used for routine examinations. Thatcher et al [12] identified a systematic analysis of the results of 88 published articles that specifically

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