Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors

Rhonda K. Yantiss, Hee Kyung Chang, Francis A. Farraye, Carolyn Compton, Robert D. Odze

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We have noted that many histologically and immunohistochemically confirmed pancreatic endocrine tumors show immunophenotypic evidence of acinar cell differentiation, but the clinical relevance of this finding is unknown. We performed this study to evaluate the prevalence and prognostic significance of exocrine differentiation by immunohistochemistry in pancreatic endocrine tumors that do not show morphologic features of acinar cell differentiation. Routinely processed tissue sections from 87 pancreatic endocrine tumors were immunohistochemically stained with monoclonal antibodies against acinar (lipase, chymotrypsin, trypsin) and endocrine cell markers (chromogranin A, neuron-specific enolase, synaptophysin, Leu-7) and for the proliferation-associated peptide Ki67. The degree of staining with each marker was graded on a three-tier scale for acinar markers (grade 0, ≅5%; grade 1, 5-10%; grade 2, 11-25%; and grade 3, >25%) and on a four-tier scale for endocrine markers (grade 0, <5%; grade 1, 5-25%; grade 2, 26-50%; grade 3, 51-75%; and grade 4, >75%), and the results were correlated with clinical outcome (mean follow-up 53 months). Greater than 75% of the tumor cells stained for chromogranin A, neuron-specific enolase, synaptophysin, and Leu-7 in 100%, 96%, 93%, and 27% of cases, respectively. Overall, 66% of tumors stained positively for at least one acinar cell marker, 31% stained for at least two acinar cell markers, and 13% stained for all three acinar cell markers. Forty-seven percent stained for lipase (23 grade 1, 11 grade 2, seven grade 3), 37% for trypsin (22 grade 1, three grade 2, seven grade 3), and 25% stained for chymotrypsin (13 grade 1, five grade 2, four grade 3). No correlation was noted between the presence or extent of expression of any single or combination of acinar cell markers and clinical outcome. However, higher tumor stage correlated with a poor clinical outcome (p = 0.002), and location in the tail of the pancreas was associated with a longer interval to tumor recurrence (p = 0.03). The presence of synaptophysin (p = 0.03) and Leu-7 expression (p = 0.03) correlated significantly with less aggressive clinical behavior. An association was observed between increased Ki67 labeling and poorer clinical outcome, but this was not statistically significant (p >0.05). In conclusion, immunophenotypic evidence of acinar cell differentiation is common in pancreatic endocrine tumors, but this feature does not have any relevance to clinical prognosis. However, in addition to tumor stage, location in the pancreatic tail and the immunohistochemical expression of synaptophysin and/or Leu-7 may be useful prognostic indicators in patients with these lesions.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume26
Issue number7
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Acinar Cells
Cell Differentiation
Synaptophysin
Neoplasms
Chromogranin A
Phosphopyruvate Hydratase
Lipase
Endocrine Cells
Chymotrypsin
Trypsin
Pancreas
Biomarkers
Immunohistochemistry
Monoclonal Antibodies
Staining and Labeling
Recurrence
Peptides

Keywords

  • Acinar cell carcinoma
  • Chromogranin A
  • Chymotrypsin
  • Immunohistochemistry
  • Ki67
  • Leu-7
  • Lipase
  • Neuron specific enolase
  • Pancreatic endocrine tumor
  • Synaptophysin
  • Trypsin

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors. / Yantiss, Rhonda K.; Chang, Hee Kyung; Farraye, Francis A.; Compton, Carolyn; Odze, Robert D.

In: American Journal of Surgical Pathology, Vol. 26, No. 7, 2002, p. 893-901.

Research output: Contribution to journalArticle

Yantiss, Rhonda K. ; Chang, Hee Kyung ; Farraye, Francis A. ; Compton, Carolyn ; Odze, Robert D. / Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors. In: American Journal of Surgical Pathology. 2002 ; Vol. 26, No. 7. pp. 893-901.
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T1 - Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors

AU - Yantiss, Rhonda K.

AU - Chang, Hee Kyung

AU - Farraye, Francis A.

AU - Compton, Carolyn

AU - Odze, Robert D.

PY - 2002

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N2 - We have noted that many histologically and immunohistochemically confirmed pancreatic endocrine tumors show immunophenotypic evidence of acinar cell differentiation, but the clinical relevance of this finding is unknown. We performed this study to evaluate the prevalence and prognostic significance of exocrine differentiation by immunohistochemistry in pancreatic endocrine tumors that do not show morphologic features of acinar cell differentiation. Routinely processed tissue sections from 87 pancreatic endocrine tumors were immunohistochemically stained with monoclonal antibodies against acinar (lipase, chymotrypsin, trypsin) and endocrine cell markers (chromogranin A, neuron-specific enolase, synaptophysin, Leu-7) and for the proliferation-associated peptide Ki67. The degree of staining with each marker was graded on a three-tier scale for acinar markers (grade 0, ≅5%; grade 1, 5-10%; grade 2, 11-25%; and grade 3, >25%) and on a four-tier scale for endocrine markers (grade 0, <5%; grade 1, 5-25%; grade 2, 26-50%; grade 3, 51-75%; and grade 4, >75%), and the results were correlated with clinical outcome (mean follow-up 53 months). Greater than 75% of the tumor cells stained for chromogranin A, neuron-specific enolase, synaptophysin, and Leu-7 in 100%, 96%, 93%, and 27% of cases, respectively. Overall, 66% of tumors stained positively for at least one acinar cell marker, 31% stained for at least two acinar cell markers, and 13% stained for all three acinar cell markers. Forty-seven percent stained for lipase (23 grade 1, 11 grade 2, seven grade 3), 37% for trypsin (22 grade 1, three grade 2, seven grade 3), and 25% stained for chymotrypsin (13 grade 1, five grade 2, four grade 3). No correlation was noted between the presence or extent of expression of any single or combination of acinar cell markers and clinical outcome. However, higher tumor stage correlated with a poor clinical outcome (p = 0.002), and location in the tail of the pancreas was associated with a longer interval to tumor recurrence (p = 0.03). The presence of synaptophysin (p = 0.03) and Leu-7 expression (p = 0.03) correlated significantly with less aggressive clinical behavior. An association was observed between increased Ki67 labeling and poorer clinical outcome, but this was not statistically significant (p >0.05). In conclusion, immunophenotypic evidence of acinar cell differentiation is common in pancreatic endocrine tumors, but this feature does not have any relevance to clinical prognosis. However, in addition to tumor stage, location in the pancreatic tail and the immunohistochemical expression of synaptophysin and/or Leu-7 may be useful prognostic indicators in patients with these lesions.

AB - We have noted that many histologically and immunohistochemically confirmed pancreatic endocrine tumors show immunophenotypic evidence of acinar cell differentiation, but the clinical relevance of this finding is unknown. We performed this study to evaluate the prevalence and prognostic significance of exocrine differentiation by immunohistochemistry in pancreatic endocrine tumors that do not show morphologic features of acinar cell differentiation. Routinely processed tissue sections from 87 pancreatic endocrine tumors were immunohistochemically stained with monoclonal antibodies against acinar (lipase, chymotrypsin, trypsin) and endocrine cell markers (chromogranin A, neuron-specific enolase, synaptophysin, Leu-7) and for the proliferation-associated peptide Ki67. The degree of staining with each marker was graded on a three-tier scale for acinar markers (grade 0, ≅5%; grade 1, 5-10%; grade 2, 11-25%; and grade 3, >25%) and on a four-tier scale for endocrine markers (grade 0, <5%; grade 1, 5-25%; grade 2, 26-50%; grade 3, 51-75%; and grade 4, >75%), and the results were correlated with clinical outcome (mean follow-up 53 months). Greater than 75% of the tumor cells stained for chromogranin A, neuron-specific enolase, synaptophysin, and Leu-7 in 100%, 96%, 93%, and 27% of cases, respectively. Overall, 66% of tumors stained positively for at least one acinar cell marker, 31% stained for at least two acinar cell markers, and 13% stained for all three acinar cell markers. Forty-seven percent stained for lipase (23 grade 1, 11 grade 2, seven grade 3), 37% for trypsin (22 grade 1, three grade 2, seven grade 3), and 25% stained for chymotrypsin (13 grade 1, five grade 2, four grade 3). No correlation was noted between the presence or extent of expression of any single or combination of acinar cell markers and clinical outcome. However, higher tumor stage correlated with a poor clinical outcome (p = 0.002), and location in the tail of the pancreas was associated with a longer interval to tumor recurrence (p = 0.03). The presence of synaptophysin (p = 0.03) and Leu-7 expression (p = 0.03) correlated significantly with less aggressive clinical behavior. An association was observed between increased Ki67 labeling and poorer clinical outcome, but this was not statistically significant (p >0.05). In conclusion, immunophenotypic evidence of acinar cell differentiation is common in pancreatic endocrine tumors, but this feature does not have any relevance to clinical prognosis. However, in addition to tumor stage, location in the pancreatic tail and the immunohistochemical expression of synaptophysin and/or Leu-7 may be useful prognostic indicators in patients with these lesions.

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KW - Immunohistochemistry

KW - Ki67

KW - Leu-7

KW - Lipase

KW - Neuron specific enolase

KW - Pancreatic endocrine tumor

KW - Synaptophysin

KW - Trypsin

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