title: Metalloproteinase-9 immunoexpression and angiogenesis in thyroid follicular neoplasms: relation to clinical and histopathologic features.
abstract: BACKGROUND
  Thyroid follicular neoplasms (adenoma and carcinoma) may pose considerable difficulties to the differential diagnosis. Because such a distinction is not possible at fine-needle aspiration, surgery is often necessary. Clinical information such as age, sex, and node size is important in case of suspected carcinoma. Follicular carcinoma is characterized by capsular invasion, vascular invasion, and metastatic dissemination mainly by the hematogenic pathway. This invasion depends on collagen degradation in capsule and in subendothelial basement membrane. Collagen degradation has been widely researched in the angiogenesis process and in the hematogenic dissemination mechanism. In this study, we performed clinical and histopathologic assessment of 74 follicular neoplasms, as well as immunohistochemical reactions for CD-34 protein to estimate angiogenesis and for metalloproteinase-9, an enzyme that degrades type IV collagen.
  
  
  METHODS
  The research was carried out retrospectively in 74 patients who had surgery and were followed up at HC-FMUSP and IBCC. Clinical, histologic, and immunohistochemical variables were compared among the groups of follicular neoplasms and a control group of 36 patients with colloid goiter.
  
  
  RESULTS
  No significant statistical difference was found between patients with follicular adenoma and thyroid follicular carcinoma concerning sex (p =.092), age (p =.098), thyroid node size (p =.426), vascularization (p =.388), and immunostaining intensity for metalloproteinase-9 (p =.055). The proportion of immunoreactive cells for metalloproteinase-9 in follicular carcinoma cases was higher than that observed in follicular adenoma cases (p <.001). Patients in more advanced stages of carcinoma were more than 45 years old (p =.006), presented extensive invasion (p <.001), had less vascularization (p =.046), and a had higher proportion of immunoreactive cells for metalloproteinase-9 (p <.001).
  
  
  CONCLUSIONS
  The proportion of immunoreactive cells for metalloproteinase-9 in follicular carcinoma was higher than that observed in follicular adenoma, with a significant statistical difference (p <.001). This method must be developed to apply in material obtained by fine-needle aspiration to differentiate follicular adenoma from carcinoma.
authors.affiliation: The Brazilian Institute For Cancer Control (IBCC) and The Head and Neck Surgery Discipline of the University of São Paulo Medical School Hospital (HC-FMUSP), Brazil. FRIGUGLI@uol.com.br
authors.forename: C U
authors.initials: CU
authors.lastname: FrigugliettI
authors.forename: E S
authors.initials: ES
authors.lastname: Mello
authors.forename: I V
authors.initials: IV
authors.lastname: Castro
authors.forename: G B
authors.initials: GB
authors.lastname: Filho
authors.forename: V A
authors.initials: VA
authors.lastname: Alves
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D008666:Metalloendopeptidases