TY - JOUR
T1 - Histomorphometric evaluation of the Ki-67 proliferation rate and CD34 microvascular and D2-40 lymphovascular densities drives the pulmonary typical carcinoid outcome
AU - de Vilhena, Alyne Fonseca
AU - das Neves Pereira, João Carlos
AU - Parra, Edwin Roger
AU - Balancin, Marcelo Luiz
AU - Ab´Saber, Alexandre
AU - Martins, Vanessa
AU - Farhat, Cecilia
AU - Abrantes, Marcelo Militao
AU - de Campos, Jose Ribas Milanez
AU - Tedde, Miguel Lia
AU - Takagaki, Teresa
AU - Capelozzi, Vera Luiza
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P =.01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P <.05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P <.05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.
AB - Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P =.01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P <.05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P <.05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.
KW - CD34
KW - Carcinoid tumors
KW - D2-40
KW - Ki-67 index
KW - Morphometry
KW - Survival
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U2 - 10.1016/j.humpath.2018.07.007
DO - 10.1016/j.humpath.2018.07.007
M3 - Article
C2 - 30031097
AN - SCOPUS:85053833892
SN - 0046-8177
VL - 81
SP - 201
EP - 210
JO - Human Pathology
JF - Human Pathology
ER -