engleski

Expression of intratumoral microvessel density in differentiated carcinomas of thyroid gland with and without metastases

Differentiated carcinoma of the thyroid is considered to be a biologically relatively indolent neoplasm characterized by a favorable outcome following appropriate surgical treatment. However, about 30% of the tumors take an unexpected course and behave in a highly malignant fashion, showing poor prognosis. Therefore, in order to investigate whether intratumoral microvessel density could be used to identify a subgroup of patients with more aggressive behavior of the tumor as potential candidates for radical surgical treatment, adjuvant radiotherapy, antiangiogenic therapy and more intensive clinical follow-up, intratumoral microvessel count (MVC) and intratumoral microvessel density (MVD) were analyzed in 50 localized papillary carcinomas (LPC), 50 papillary carcinomas of the thyroid gland with metastatic involvement of regional lymph nodes (PCMLN), 50 associated metastatic tumors (M), and normal thyroid gland tissue. Also, intratumoral MVD and tumor histologic grade were compared between LPC and PCMLN groups, and the relationship between intratumoral MVD and clinical parameters of age, sex and tumor size was analyzed. The study was carried out by immunohistochemistry on the paraffin embedded material. Formalin fixed, paraffin embedded tissue was cut at 5 mm, deparaffinized and stained with monoclonal antibody to human Von Willebrand Factor H0079 (Factor VIII related antigen, Dako, Denmark) following Microwave Streptavidin ImmunoPeroxidase (MSIP) protocol on DAKO TechMateTM Horizon automated immunostainer. Invasive tumors were often heterogeneous with respect to the amount and distribution of microvessels, therefore sections were examined at low magnifications (x40, x100) to identify the most vascular area of the tumor ('hot spot'). Within these 'hot spots' counting was done in 10 non-overlapping consecutive high power magnification fields (x400/0.144 mm2). The average MVC was calculated from 10 vascular 'hot spots', and was also expressed as MVD/mm2 of the tumor area. Statistical analysis was performed by the SAS 6.12 and STATISTICA 6.0 statistical package. The level of significance was set at p<0.05 in all cases. A statistically significant difference in MVD was observed between LPC and PCMLN (p<0.001). Mean MVD in LPC was 118.00/mm2 as compared with 201.29/mm2 in PCMLN. A statistically significant difference was observed in MVD between G1 (low grade) and G2 (high grade) papillary carcinomas (p<0.001). Mean MVD in G1 carcinomas was 132.14/mm2 as compared with 208.53/mm2 in G2 carcinomas. Finally, our results suggest that intratumoral MVD expression in papillary carcinomas of the thyroid gland may help identify the group of high risk patients with a more aggressive biologic behavior of these tumors, who can benefit from new therapies such as angiogenesis-inhibiting drugs and adjuvant radiotherapy following more extensive surgical treatment, accompanied by careful follow-up. This selective approach may lead to the prevention of unnecessarily aggressive treatments for tumors that are likely to take a benign course and of inappropriate therapy for others with anticipated aggressive behavior display.

Carcinomas of thyroid glands; micvrovessel; factor VIII

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