Canine pancreatic neuroendocrine tumors were studied using different image analysis techniques (nuclear image histometry, analysis of argyrophilic proteins of nucleolar organizer regions, determination of the mouse anti-Ki 67 antigen proliferation index, and DNA densitometry) to correlate their biological behavior with objective phenotypic markers. The methods were compared to determine the best method for distinguishing between metastatic and nonmetastatic tumors. Discrimination between the two types of tumor was possible using nuclear image histometry in combination with morphometric analysis of argyrophilic proteins of nucleolar organizer regions. In contrast, the mouse anti-Ki 67 antigen proliferation index, DNA measurement, and immunohistochemical parameters revealed no significant difference between the two types of tumors.
AubeleMAuerGGaisPJüttingURodenackerKVossA:
Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma: comparison with classifications and prognosis.
Pathol Res Pract190:129–137, 1994
4.
AzizDCBarathurRB:
Quantitation and morphometric analysis of tumors by image analysis.
J Cell Biochem19(Suppl):120–125, 1994
BestettiGRossiGL:
Islet cell carcinomas in dogs.
Virchows Arch [A]405:203–214, 1985
7.
BurgerGAubeleMClasenBJüttingUGaisPRodenackerK:
Malignancy associated changes in squamous epithelium of the head and neck region.
Anal Cell Pathol7:181–193, 1994
8.
CapellaCHeitzPUHöflerHSolciaEKlöppelG:
Revised classification of neuroendocrine tumors of the lung, pancreas and gut.
Virchows Arch425:547–560, 1995
9.
CaywoodDDKlausnerJSO'LearyTPWithrowSJRichardsonRCHarveyHJNorrisAMHendersonRAJohnstonSD:
Pancreatic insulin-secreting neoplasms: clinical, diagnostic, and prognostic features in 73 dogs.
J Am Anim Hosp Assoc24:578–584, 1987
10.
Diest vanPBaakJPAMatze-CokPWisse-BrekelmansECMvan GalenCMKurverPHJBellotSMFijnheerJvan GorpLHMKweeWSLosJPeterseJLRuitenbergHMSchapersRFMSchipperMEISomsenJGWilligAWPMAriensAT:
Reproducibility of mitosis counting in 2469 breast cancer specimens: results from the multicentre morphometric mammary carcinoma project.
Hum Pathol23:603–607, 1992
11.
DonowCBaischHHeitzPUKlöppelG:
Nuclear DNA content in 27 pancreatic endocrine tumors: correlation with malignancy, survival and expression of glycoprotein hormone alpha chain.
Virchows Arch [A]419:463–468, 1991
12.
DunnJKBostockDEHerrtageMEJacksonKFWalkerMJ:
Insulin-secreting tumours of the canine pancreas: clinical and pathological features of 11 cases.
J Small Anim Pract34:325–331, 1993
13.
EganMJCrockerJ:
Nucleolar organiser regions in pathology.
Br J Cancer65:1–7, 1992
14.
ErikssonBÖbergKWilanderEBenttssonARisbergBLindgrenPGAnderssonT:
Nuclear DNA distribution in neuroendocrine gastroenteropancreatic tumors before and during treatment.
Acta Oncol28:193–197, 1989
15.
FalkmerUGFalkmerS:
The value of cytometric DNA analysis as a prognostic tool in neuroendocrine neoplastic diseases.
Pathol Res Pract191:281–303, 1995
16.
Graeme-CookFBellDAFlotteTJPrefferFPastel-LevyCNardiGComptonCC:
Aneuploidy in pancreatic insulinomas does not predict malignancy.
Cancer66:2365–2368, 1990
17.
HallPALevisonDA:
Review: assessment of cell proliferation.
J Clin Pathol43:184–192, 1990
18.
HamiltonPWAllenDC:
Morphometry in histopathology.
J Pathol175:369–379, 1995
19.
HaroskeGMeyerWDimmerVKunzeKDTheissigF:
Feasibility and limitations of a cytometric DNA ploidy analysis procedure in tissue sections.
Zentralbl Pathol139:407–417, 1993
20.
HawkinsKLSummersBAKuhajdaFPSmithCA:
Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs.
Vet Pathol24:170–179, 1987
Herbay vonASiegBSchürmannGHofmannWJBetzlerMOttoHF:
Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations.
Gut32:949–953, 1991
23.
HermanekPSobinLH:
TNM Classification of Malignant Tumours,
4th ed., pp. 1–12.
Springer, New York, NY, USA,
1987
24.
HermannsWLiebigKSchulzPC:
Postembedding immunohistochemical demonstration of antigen in experimental polyarthritis using plastic embedded whole joints.
Histochemistry37:439–446, 1981
25.
HöflerHRuhriCPützBWinsbergerGHauserH:
Oncogene expression in endocrine tumours.
Virchows Arch [B]55:355–361, 1988
26.
HuMK:
Visual pattern recognition by moment invariants.
IRE Trans Inform Theory8:179–187, 1962
27.
HubbelHRHsuTC:
Identification of nucleolar organizer regions (NORs) in normal and neoplastic cells by silver staining technique.
Cytogenet Cell Genet19:185–196, 1977
28.
InoueCShigaKTakasawaSKitagawaMYamamotoHOkamotoH:
Evolutionary conservation of the insulinoma gene rig and its possible function.
Proc Natl Acad Sci USA84:6659–6662, 1987
29.
IshidoTItabashiMOchiaiAHirotaTYokotaTSaitoD:
Morphometric analysis of colorectal dysplasia with image processing.
Arch Pathol Lab Med118:619–623, 1994
30.
JubbKVF:
The pancreas. In:
Pathology of Domestic Animals,
ed. JubbKVFKennedyPCand PalmerN,
4th ed.,
vol. 2, pp. 407–424.
Academic Press, London, UK,
1993
31.
KennyBDSloanJMHamiltonPWWattPCHJohnstonCFBuchananKD:
The role of morphometry in predicting prognosis in pancreatic islet cell tumors.
Cancer64:460–465, 1989
32.
KlöppelGHeitzPU:
Pancreatic endocrine tumors.
Pathol Res Pract183:155–168, 1988
33.
LeiferCE:
Peterson ME, Matus RE: Insulin-secreting tumor: diagnosis and medical and surgical treatment in 55 dogs.
J Am Vet Med Assoc188:60–64, 1986
34.
LukiniusAWilanderEWestermarkGTEngströmUWestermarkP:
Co-localisation of islet amyloid polypeptid and insulin in the B cell secretory granules of the human pancreatic islets.
Diabetologia32:240–244, 1989
35.
MehlhaffCJPetersonMEPatnaikAKCarilloJM:
Insulin-producing islet cell neoplasms: surgical considerations and general management in 35 dogs.
J Am Anim Hosp Assoc21:607–612, 1985
36.
MollRCowinPKapprellHPFrankeWW:
Desmosomal proteins: new markers for identification and classification of tumors.
Lab Invest54:4–25, 1986
37.
MooreFMDayalYSheltonJC:
Pancreatic endocrine tumors in dogs: an immunohistochemical analysis.
Lab Invest52:44A–45A, 1985 [Abstract]
38.
MukaiKGrottingJCGreiderMHRosaiJ:
Retrospective study of 77 endocrine tumors using the immunoperoxidase method.
Am J Surg Pathol6:387–399, 1982
39.
O'BrienTDHaydenDWO'LearyTPCaywoodDDJohnsonKH:
Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid.
Vet Pathol24:308–314, 1987
40.
PelosiGZamboniGDoglioniCRodellaSBresaolaEIaconoCSerioGIannucciAScarpaA:
Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas.
Am J Surg Pathol16:1215–1225, 1992
41.
PohlNNSwartzFJCarstensPHB:
Polyploidy in islets of normal and diabetic humans.
Hum Pathol12:184–186, 1981
42.
RodenackerKAubeleMBurgerGGaisPJüttingUGössnerWOberholzerM:
Cytometry in histological sections of colon carcinoma.
Pathol Res Pract188:556–560, 1992
43.
RüschoffJWillemerSKlöppelGArnoldRThomasC:
AgNOR und alpha-HCG Bestimmung als Malignitätsmarker bei neuroendokrinen Tumoren des Pankreas und Dünndarms.
Verh Dtsch Ges Pathol74:502, 1990
44.
ShigaKYamamotoHOkamotoH:
Isolation and characterization of the human homologue of rig and its pseudogenes: the functional gene has features characteristic of housekeeping genes.
Proc Natl Acad Sci USA87:3594–3598, 1990
45.
SogaJTazawaK:
Pathologic analysis of carcinoids.
Cancer28:990–998, 1971
46.
StefaniniPCarboniMPatrassiNBosoliA:
Beta-islet cell tumors of the pancreas: results of a study on 1,067 cases.
Surgery75:597–609, 1974
47.
StipaFArganiniMBibboMStrausFIIDytchHWiedGHorvathKKaplanEL:
Nuclear DNA analysis of insulinomas and gastrinomas.
Surgery102:988–998, 1987
48.
TosiPLuziPBaakJPAMiraccoCSantopietroRVindigniCMatteiFMAcconciaAMassaiMR:
Nuclear morphometry as an important prognostic factor in stage I renal cell carcinoma.
Cancer58:2512–2518, 1986
49.
WestermarkPGirmeliusLPolakJMLarssonLIVan NoordenSWilanderEPearseAGE:
Amyloid in polypeptide hormone-producing tumors.
Lab Invest37:212–215, 1977
50.
WilanderEGrimeliusL:
Identification, characterization and classification of endocrine tumours.
Zentralbl Pathol139:95–100, 1993
51.
ZbieranowskiIMurrayD:
The study of endocrine tumors by flow and image cytometry.
Endocr Pathol3:63–82, 1992
