Novel finding of paired box 5 (PAX5) cytoplasmic staining in well-differentiated rectal neuroendocrine tumors (Carcinoids) and its diagnostic and potentially prognostic utility

Zhiyan Fu, Chunlai Zuo, Christine E. Sheehan, Deepa T. Patil, Jingmei Lin, Zhaohai Yang, Hwajeong Lee

Research output: Contribution to journalArticle

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Abstract

Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver. Representative tumor sections were subject to immunohistochemical stain for PAX5 antibody. Immunohistochemistry for 3 L-cell markers, glucagon-like peptide 1 and 2, and peptide YY, was performed on all rectal and appendiceal NETs and all other NETs with cytoplasmic PAX5 staining. Cytoplasmic PAX5 staining was observed in 90% (19/21) of rectal NET, 27% (3/11) of appendiceal, 14% (2/14) of pancreatic, 7% (2/29) of lung, 25% (3/12) metastatic NET in the liver, and 100% (1/1) of renal NET. No PAX5 cytoplasmic staining was seen in all grades of NET in other organs, rectal WD-NET G3, and all neuroendocrine carcinoma. L-cell marker staining was observed in all 21 (100%) rectal, in 3 of 3 (100%) PAX5-positive, and 1 of 7 (14%) PAX5-negative appendiceal NET. Cytoplasmic PAX5 staining is specific for rectal carcinoids. The sensitivity and specificity of PAX5 to detect L-cell type rectal carcinoids is 90% (19/21) and 100% (21/21), respectively. Cytoplasmic localization of the PAX5 protein may be utilized as a surrogate marker to detect L-cell type rectal carcinoids.

Original languageEnglish (US)
Pages (from-to)454-460
Number of pages7
JournalApplied Immunohistochemistry and Molecular Morphology
Volume27
Issue number6
DOIs
StatePublished - Jul 1 2019
Externally publishedYes

Fingerprint

Neuroendocrine Tumors
Carcinoid Tumor
Rectal Neoplasms
Staining and Labeling
PAX5 Transcription Factor
Neuroendocrine Carcinoma
Glucagon-Like Peptide 2
Peptide YY
Glucagon-Like Peptide 1
Liver
Gastrointestinal Tract
Coloring Agents
Biomarkers
Immunohistochemistry
Kidney
Sensitivity and Specificity
Lung
Antibodies

Keywords

  • carcinoid
  • L-cell
  • neuroendocrine
  • PAX5
  • rectum

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

Cite this

Novel finding of paired box 5 (PAX5) cytoplasmic staining in well-differentiated rectal neuroendocrine tumors (Carcinoids) and its diagnostic and potentially prognostic utility. / Fu, Zhiyan; Zuo, Chunlai; Sheehan, Christine E.; Patil, Deepa T.; Lin, Jingmei; Yang, Zhaohai; Lee, Hwajeong.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 27, No. 6, 01.07.2019, p. 454-460.

Research output: Contribution to journalArticle

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abstract = "Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver. Representative tumor sections were subject to immunohistochemical stain for PAX5 antibody. Immunohistochemistry for 3 L-cell markers, glucagon-like peptide 1 and 2, and peptide YY, was performed on all rectal and appendiceal NETs and all other NETs with cytoplasmic PAX5 staining. Cytoplasmic PAX5 staining was observed in 90{\%} (19/21) of rectal NET, 27{\%} (3/11) of appendiceal, 14{\%} (2/14) of pancreatic, 7{\%} (2/29) of lung, 25{\%} (3/12) metastatic NET in the liver, and 100{\%} (1/1) of renal NET. No PAX5 cytoplasmic staining was seen in all grades of NET in other organs, rectal WD-NET G3, and all neuroendocrine carcinoma. L-cell marker staining was observed in all 21 (100{\%}) rectal, in 3 of 3 (100{\%}) PAX5-positive, and 1 of 7 (14{\%}) PAX5-negative appendiceal NET. Cytoplasmic PAX5 staining is specific for rectal carcinoids. The sensitivity and specificity of PAX5 to detect L-cell type rectal carcinoids is 90{\%} (19/21) and 100{\%} (21/21), respectively. Cytoplasmic localization of the PAX5 protein may be utilized as a surrogate marker to detect L-cell type rectal carcinoids.",
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AU - Fu, Zhiyan

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AU - Sheehan, Christine E.

AU - Patil, Deepa T.

AU - Lin, Jingmei

AU - Yang, Zhaohai

AU - Lee, Hwajeong

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AB - Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver. Representative tumor sections were subject to immunohistochemical stain for PAX5 antibody. Immunohistochemistry for 3 L-cell markers, glucagon-like peptide 1 and 2, and peptide YY, was performed on all rectal and appendiceal NETs and all other NETs with cytoplasmic PAX5 staining. Cytoplasmic PAX5 staining was observed in 90% (19/21) of rectal NET, 27% (3/11) of appendiceal, 14% (2/14) of pancreatic, 7% (2/29) of lung, 25% (3/12) metastatic NET in the liver, and 100% (1/1) of renal NET. No PAX5 cytoplasmic staining was seen in all grades of NET in other organs, rectal WD-NET G3, and all neuroendocrine carcinoma. L-cell marker staining was observed in all 21 (100%) rectal, in 3 of 3 (100%) PAX5-positive, and 1 of 7 (14%) PAX5-negative appendiceal NET. Cytoplasmic PAX5 staining is specific for rectal carcinoids. The sensitivity and specificity of PAX5 to detect L-cell type rectal carcinoids is 90% (19/21) and 100% (21/21), respectively. Cytoplasmic localization of the PAX5 protein may be utilized as a surrogate marker to detect L-cell type rectal carcinoids.

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