Comparison of PCR-based detection of chromogranin A mRNA with traditional histological lymph node staging of small intestinal neuroendocrine neoplasia

BMC Research Notes

Irvin Modlin²  Mark Kidd²  Jaroslaw Jedrych¹  Andrea Barbieri¹  Daniele Alaimo²  Simon Schimmack²  Bernhard Svejda²  Barton Kenney¹  Ben Lawrence² 

[1] Department of Pathology, Division of Gastrointestinal and Hepatic Pathology, Yale University School of Medicine, 208023, New Haven, CT, USA;Gastrointestinal Pathobiology Research Group, Yale University School of Medicine, 208602, New Haven, CT, USA

关键词: Staging;    RNA;    Neuroendocrine neoplasm;    Neuroendocrine tumor;    Micrometastasis;    Metastasis;    Lymph node;    Histopathology;    Immunohistochemistry;    Chromogranin A;   

Others  :  1166241
DOI  :  10.1186/1756-0500-5-318

 received in 2012-02-28, accepted in 2012-05-25,  发布年份 2012

【 摘 要 】

Background

Accurate neuroendocrine neoplasia (NEN) staging is vital for determining prognosis and therapeutic strategy. The great majority of NENs express chromogranin A (CgA) which can be detected at a protein or transcript level. The current standards for lymph node metastasis detection are histological examination after Hematoxylin and Eosin (H&E) and CgA immunohistochemical (IHC) staining. We hypothesized that detection of CgA mRNA transcripts would be a more sensitive method of detecting these metastases.

Findings

We compared these traditional methods with PCR for CgA mRNA extracted from formalin fixed paraffin embedded slides of lymph nodes (n = 196) from small intestinal NENs, other gastrointestinal cancers and benign gastrointestinal disease. CgA PCR detected significantly more NEN lymph nodes (75%) than H&E (53%) or CgA IHC (57%) (p = 0.02). PCR detected CgA mRNA in 50% (14 of the 28) of SI-NEN lymph nodes previously considered negative. The false positive rate for detection of CgA mRNA was 19% in non-neuroendocrine cancers, and appeared to be due to occult neuroendocrine differentiation or contamination by normal epithelium during histological processing.

Conclusions

Molecular pathological analysis demonstrates the limitations of observer-dependent histopathology. CgA PCR analysis detected the presence of CgA transcripts in lymph nodes without histological evidence of tumor metastasis. Molecular node positivity (stage _molN1) of SI-NEN lymph nodes could confer greater staging accuracy and facilitate early and accurate therapeutic intervention. This technique warrants investigation using clinically annotated tumor samples with follow-up data.

【 授权许可】

   
2012 Lawrence et al.; licensee BioMed Central Ltd.

【 图 表 】

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