Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway.
BACKGROUND
The link between inflammation and cancer is well-established, but the link between Hashimoto thyroiditis (HT) and thyroid cancer remains controversial. The purpose of our study was to determine the incidence of patients with thyroid cancer and associated HT at our institution, to correlate our patient population demographics with the Surveillance, Epidemiology and End Results (SEER) database, and to assess the expression of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in patients with HT.


METHODS
Demographic and histologic data were collected from patients undergoing thyroid resection at the University of Texas Medical Branch from 1987 to 2002 and compared with the SEER database. Immunohistochemistry for phosphorylated Akt (a marker of PI3K activity), Akt isoforms and PTEN (an inhibitor of PI3K) was performed on paraffin-embedded blocks of resected thyroid tissue.


RESULTS
Our patient population demographics and thyroid cancer incidence by histologic type were similar to patients in the SEER database. Ninety-eight (37.7%) resected specimens had pathologic changes consistent with HT; 43 (43.8%) had an associated well-differentiated thyroid cancer. Increased phosphorylated Akt, Akt1, and Akt2 expression was noted in regions of HT and thyroid cancer compared with regions of normal surrounding thyroid tissue.


CONCLUSIONS
Patients with HT were three times more likely to have thyroid cancer, suggesting a strong link between chronic inflammation and cancer development. PI3K/Akt expression was increased in both HT and well-differentiated thyroid cancer, suggesting a possible molecular mechanism for thyroid carcinogenesis.
Larson
Shawn D
SD
Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0536, USA.
Jackson
Lindsey N
LN
Riall
Taylor S
TS
Uchida
Tatsuo
T
Thomas
Robert P
RP
Qiu
Suimin
S
Evers
B Mark
BM
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D005260:Female; D050031:Hashimoto Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D018426:SEER Program; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D014481:United States / Q000453:epidemiology
D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase