Comparison of PAX6 and PAX8 as Immunohistochemical Markers for Pancreatic Neuroendocrine Tumors

Lai, Jinping; Mertens, Richard B.; Mirocha, James; Koo, Jamie; Venturina, Mariza; Chung, Fai; Mendez, Allen B.; Kahn, Melissa; Dhall, Deepti

doi:10.1007/s12022-014-9346-3

Cited by 35 publications

(24 citation statements)

References 15 publications

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“…The latter included markers commonly used in surgical pathology practice to demonstrate an origin from epithelia of the breast (gross cystic disease fluid protein‐15 (GCDFP‐15), estrogen receptor (ER)), Müllerian system (paired box 8 (PAX‐8), ER), lung (Napsin A, thyroid transcription factor‐1 (TTF‐1)), kidney (PAX‐8, Napsin A), liver (hepatocyte paraffin 1 (HepPar1)), salivary gland (GCDFP‐15), and thyroid (PAX‐8, TTF‐1) . As 100% of pituitary adenomas are immunoreactive for synaptophysin and chromogranin, the analysis also included TTF‐1, which may be positive in both pulmonary and extrapulmonary neuroendocrine carcinomas, as well as PAX‐8, which has been reported in a subset of metastatic neuroendocrine tumors . The spectrum of immunoreactivities for each of these markers was examined in 40 pituitary adenomas, sub‐classified by available clinical data and immunophenotype.…”

Section: Introductioncontrasting

confidence: 68%

“…12 As 100% of pituitary adenomas are immunoreactive for synaptophysin and chromogranin, 10 the analysis also included TTF-1, which may be positive in both pulmonary and extrapulmonary neuroendocrine carcinomas, 18,19 as well as PAX-8, which has been reported in a subset of metastatic neuroendocrine tumors. 20 The spectrum of immunoreactivities for each of these markers was examined in 40 pituitary adenomas, subclassified by available clinical data and immunophenotype.…”

Section: Introductionmentioning

confidence: 99%

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Epithelial and organ‐related marker expression in pituitary adenomas

et al. 2016

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The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20.

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Section: Introductioncontrasting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Epithelial and organ‐related marker expression in pituitary adenomas

et al. 2016

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“…In this setting, a panel of site-specific lineage markers (TTF-1 for pulmonary origin, CDX2 for gastrointestinal tract origin, PAX8/PAX6 for gastropancreatic and duodenal origin, and ER/PR, mammaglobin, GCDFP-15 and GATA3 for mammary origin) may be helpful in distinguishing metastatic neuroendocrine neoplasms (particularly well-differentiated neuroendocrine tumors) from invasive mammary carcinomas with neuroendocrine differentiation. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] In this study, CDX2 was positive in all examined metastatic neuroendocrine neoplasms of small bowel origin, TTF-1 was positive in 70% of examined metastatic neuroendocrine neoplasms of lung origin, and ER and GATA3 were positive in 91 and 100% of invasive mammary carcinomas with neuroendocrine differentiation, respectively. Similarly, in the study by Perry et al 9 (which with the exception of one high-grade neuroendocrine carcinoma consisted entirely of well-differentiated neuroendocrine tumors), all metastatic neuroendocrine neoplasms from the gastrointestinal tract expressed CDX2 and 60% of tumors originating from the lung expressed TTF-1.…”

Section: Discussionmentioning

confidence: 81%

Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation

et al. 2016

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Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well-differentiated neuroendocrine tumors often showed immunoreactivity for site-specific markers. Although the histologic and immunohistochemical features of a breast tumor may raise the suspicion of a metastatic neuroendocrine neoplasm, the pathologic findings should be interpreted in the context of the clinical history and imaging findings in order to establish an accurate diagnosis. Metastases to the breast are unusual, comprising less than 1% of all malignant neoplasms of the breast. [1][2][3][4][5] The majority of the metastatic lesions originate from the contralateral breast or hematopoietic malignancies. 1,2,5 Stomach, kidney, ovary, lung, and skin are the other common primary sites. [1][2][3][4][5] Metastatic neuroendocrine neoplasms to the breast are rare and comprise only 1-2% of all metastatic tumors to the breast. To the best of our knowledge, less than 50 cases have been described to date, primarily in the form of isolated case reports and rare case series. Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with in situ ...

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“…232 Therefore, polyclonal antibodies should be used if PAX8 is included in the workup panel and monoclonal anti-PAX8 antibodies will not work. In fact, Lai et al 231 have shown similarly high detection rates for pancreatic, duodenal and rectal NETs when a monoclonal anti-PAX6 antibody is used.…”

Section: Grading Neuroendocrine Neoplasms By Ki-67mentioning

confidence: 93%

“…223,224,[229][230][231] It is positive in 7% to 22% of gastric, appendiceal, and colonic NETs, and has been consistently negative in jejunoileal NETs. The reported frequency of positivity in pulmonary NETs ranges from 0% to 23%.…”

Section: Grading Neuroendocrine Neoplasms By Ki-67mentioning

confidence: 99%

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

Wang¹,

Kim²,

Koo³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Objectives.— To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. Data Sources.— Data sources include literature review, authors' research data, and personal practice experience. Conclusions.— Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.

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Comparison of PAX6 and PAX8 as Immunohistochemical Markers for Pancreatic Neuroendocrine Tumors

Cited by 35 publications

References 15 publications

Epithelial and organ‐related marker expression in pituitary adenomas

Epithelial and organ‐related marker expression in pituitary adenomas

Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

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