Home LiteratureArticle Details
PMID: 9916927 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Familial adenomatous polyposis-associated thyroid cancer: a clinical, pathological, and molecular genetics study.

The American journal of pathology ·Vol. 154 ·No. 1 ·1999-01-00 ·Pages 127-35

Soravia C, Sugg SL, Berk T, Mitri A, Cheng H, Gallinger S, Cohen Z, Asa SL, Bapat BV

Abstract

We report two familial adenomatous polyposis (FAP) kindreds with thyroid cancer, harboring two apparently novel germlineAPC mutations. The clinical phenotype in the first kindred was typical of classical adenomatous polyposis, whereas the second kindred exhibited an attenuated adenomatous polyposis phenotype. There was a female predominance with a mean age of 34 years (range, 23-49) at cancer diagnosis. Multiple sections of four thyroid tumors from three FAP patients were analyzed in detail. Histological examination of thyroid tumors showed a range of morphological features. Some tumors exhibited typical papillary architecture and were associated with multifocal carcinoma; in others, there were unusual areas of cribriform morphology, and spindle-cell components with whorled architecture. Immunoreactivity for thyroglobulin and high molecular weight keratins was strong. Somatic APC mutation analysis revealed an insertion of a novel long interspersed nuclear element-1-like sequence in one tumor sample, suggesting disruption of APC. In three FAP patients, ret/PTC-1 and ret/PTC-3 were expressed in thyroid cancers. No positivity was observed for ret/ PTC-2. p53 immunohistochemistry was positive in only one section of a recurrent thyroid tumor sample. Our data suggest that genetic alterations in FAP-associated thyroid cancer involve loss of function of APC along with the gain of function of ret/PTC, while alterations of p53 do not appear to be an early event in thyroid tumorigenesis.

MeSH Terms
Adenomatous Polyps/complications,genetics Adult Drosophila Proteins Female Germ-Line Mutation/genetics Humans Immunohistochemistry Male Middle Aged Molecular Biology/methods Nuclear Receptor Coactivators Oncogene Proteins/genetics Oncogene Proteins, Fusion/genetics Protein-Tyrosine Kinases Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases/metabolism Thyroid Neoplasms/complications,genetics,metabolism,pathology Transcription Factors
Chemicals
Drosophila Proteins NCOA4 protein, human Nuclear Receptor Coactivators Oncogene Proteins Oncogene Proteins, Fusion Proto-Oncogene Proteins Transcription Factors Protein-Tyrosine Kinases Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila ret-PTC fusion oncoproteins, human
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Soravia C
Department of Surgery, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, University of Toronto, Canada.
Sugg S L
Berk T
Mitri A
Cheng H
Gallinger S
Cohen Z
Asa S L
Bapat B V
References (45)
45 references, click to expand
  1. Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior.
    Endocr Pathol. 1997 Spring;8(1):21-28 PMID: 12114668
  2. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis.
    Am J Hum Genet. 1953 Jun;5(2):139-47 PMID: 13065261
  3. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.
    Cancer Res. 1992 Feb 1;52(3):643-5 PMID: 1310068
  4. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.
    Cancer Res. 1992 Jul 15;52(14):4055-7 PMID: 1319838
  5. Screening for germ-line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients.
    Hum Mutat. 1992;1(6):467-73 PMID: 1338764
  6. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.
    Hum Mol Genet. 1992 Jul;1(4):229-33 PMID: 1338904
  7. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases.
    Dis Colon Rectum. 1959 Sep-Oct;2:465-8 PMID: 13839882
  8. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum.
    Am J Hum Genet. 1951 Jun;3(2):167-76 PMID: 14902760
  9. Identification and characterization of the familial adenomatous polyposis coli gene.
    Cell. 1991 Aug 9;66(3):589-600 PMID: 1651174
  10. Identification of FAP locus genes from chromosome 5q21.
    Science. 1991 Aug 9;253(5020):661-5 PMID: 1651562
  11. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  12. Adenomatous polyposis: an association with carcinoma of the thyroid.
    Br J Surg. 1987 May;74(5):377-80 PMID: 3036290
  13. Association of endocrine neoplasia with multiple polyposis of the colon.
    Cancer. 1983 Mar 15;51(6):1171-5 PMID: 6129922
  14. Genetics of non-medullary thyroid cancer.
    QJM. 1995 Oct;88(10):685-93 PMID: 7493165
  15. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm.
    Histopathology. 1994 Dec;25(6):549-61 PMID: 7698732
  16. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444.
    Hum Mol Genet. 1995 Mar;4(3):337-40 PMID: 7795585
  17. Evidence against involvement of APC mutation in papillary thyroid carcinoma.
    Eur J Cancer. 1994;30A(7):984-7 PMID: 7946597
  18. Mutations of the adenomatous polyposis coli gene in sporadic thyroid neoplasms.
    J Clin Endocrinol Metab. 1994 Nov;79(5):1317-21 PMID: 7962323
  19. Analysis of adenomatous polyposis coli gene in thyroid tumours.
    Br J Cancer. 1994 Dec;70(6):1085-8 PMID: 7981058
  20. Mutations of the APC (adenomatous polyposis coli) gene.
    Hum Mutat. 1993;2(6):425-34 PMID: 8111410
  21. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis.
    Gut. 1993 Oct;34(10):1394-6 PMID: 8244108
  22. Molecular diagnosis of familial adenomatous polyposis.
    N Engl J Med. 1993 Dec 30;329(27):1982-7 PMID: 8247073
  23. Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.
    Cell. 1993 Dec 3;75(5):959-68 PMID: 8252631
  24. Identification of somatic APC gene mutations in periampullary adenomas in a patient with familial adenomatous polyposis (FAP).
    Hum Mol Genet. 1993 Nov;2(11):1957-9 PMID: 8281160
  25. Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma. A case report and review of the literature.
    Dig Dis Sci. 1993 Jan;38(1):185-90 PMID: 8420756
  26. Genotype-phenotype correlations of new causative APC gene mutations in patients with familial adenomatous polyposis.
    J Med Genet. 1995 Sep;32(9):728-31 PMID: 8544194
  27. APC gene: database of germline and somatic mutations in human tumors and cell lines.
    Nucleic Acids Res. 1996 Jan 1;24(1):121-4 PMID: 8594558
  28. Sisters with familial adenomatous polyposis affected with thyroid carcinoma, desmoid tumour and duodenal polyposis.
    Br J Surg. 1996 Feb;83(2):228 PMID: 8689172
  29. ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?
    J Clin Endocrinol Metab. 1996 Sep;81(9):3360-5 PMID: 8784097
  30. Association between thyroid cancer of cribriform variant and familial adenomatous polyposis.
    J Clin Pathol. 1996 Jul;49(7):611-3 PMID: 8813970
  31. Database of mutations in the p53 and APC tumor suppressor genes designed to facilitate molecular epidemiological analyses.
    Hum Mutat. 1996;7(3):202-13 PMID: 8829653
  32. Thyroid carcinoma as first manifestation of familial adenomatous polyposis.
    Neth J Med. 1996 Sep;49(3):116-8 PMID: 8854675
  33. Lessons from hereditary colorectal cancer.
    Cell. 1996 Oct 18;87(2):159-70 PMID: 8861899
  34. Papillary thyroid carcinoma in three siblings with familial adenomatous polyposis.
    Int J Colorectal Dis. 1996;11(1):34-7 PMID: 8919339
  35. Familial adenomatous polyposis in a 5 year old child: a clinical, pathological, and molecular genetic study.
    J Med Genet. 1996 Feb;33(2):157-60 PMID: 8929955
  36. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
    Science. 1997 Mar 21;275(5307):1784-7 PMID: 9065401
  37. Stabilization of beta-catenin by genetic defects in melanoma cell lines.
    Science. 1997 Mar 21;275(5307):1790-2 PMID: 9065403
  38. [Familial adenomatous polyposis and thyroid cancer].
    Gastroenterol Clin Biol. 1997;21(1):74-7 PMID: 9091394
  39. Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC): a review of clinical, genetic and therapeutic aspects.
    Schweiz Med Wochenschr. 1997 Apr 19;127(16):682-90 PMID: 9140167
  40. Is screening for thyroid carcinoma indicated in familial adenomatous polyposis? The Leeds Castle Polyposis Group.
    Int J Colorectal Dis. 1997;12(4):240-2 PMID: 9272455
  41. Thyroid carcinoma associated with familial adenomatous polyposis.
    Histopathology. 1997 Sep;31(3):231-6 PMID: 9354893
  42. The ret/ptc1 oncogene is activated in familial adenomatous polyposis-associated thyroid papillary carcinomas.
    J Clin Endocrinol Metab. 1998 Mar;83(3):1003-6 PMID: 9506763
  43. Genotype-phenotype correlations in attenuated adenomatous polyposis coli.
    Am J Hum Genet. 1998 Jun;62(6):1290-301 PMID: 9585611
  44. The impact of L1 retrotransposons on the human genome.
    Nat Genet. 1998 May;19(1):19-24 PMID: 9590283
  45. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia.
    J Clin Endocrinol Metab. 1998 Nov;83(11):4116-22 PMID: 9814501
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65259-5
Published
1999-01-00
Pages
127-35
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1853451
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65259-5 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2