Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy

Author(s)

Antonangelo, Leila ^[1] ; Tuma, Taila ^[1] ; Fabro, Alexandre ^[1] ; Acencio, Milena ^[2] ; Terra, Ricardo ^[2] ; Parra, Edwin ^[1] ; Vargas, Francisco ^[2] ; Takagaki, Teresa ^[2] ; Capelozzi, Vera ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Pathol, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Div Pulm, Inst Heart, Clin Hosp, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: Experimental Biology and Medicine; v. 241, n. 11, p. 1159-1168, JUN 2016.
• Web of Science Citations: 2

Abstract

Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC. (AU)

• FAPESP's process: 13/14277-4 - Prognosis and clinical evolution of new and current genetic and proteic biomarkers in lung cancer
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/52095-0 - Evaluation of the frequency of EGFR, KRAS and EML4-ALK mutation in adenocarcinomas and their subtypes and impact of expression of hyaluronidases and hyaluronic acid synthase in pre-neoplastic lung lesions
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Regular Research Grants