Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy. Issue 11 (June 2016)

• Record Type: Journal Article
• Authors: Antonângelo, Leila; Tuma, Taila; Fabro, Alexandre; Acencio, Milena; Terra, Ricardo; Parra, Edwin; Vargas, Francisco; Takagaki, Teresa; Capelozzi, Vera
• Is Part Of: Experimental biology and medicine. Volume 241:Issue 11(2016)
• Page Start: 1159
• Page End: 1168
• Publication Date: 2016-06
• Subjects: Lung adenocarcinoma -- inhibitors of DNA binding/inhibitors of differentiation -- angiogenesis -- immunohistochemistry -- morphometry -- prognosis; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370216632623
• Languages: English
• ISSNs: 1535-3702

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.