title: 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.
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.
authors: Department of Pathology, University of Sao Paulo, Sao Paulo 01246903,Brazil.
authors: Leila
authors: L
authors: Antonângelo
authors: Department of Pathology, University of Sao Paulo, Sao Paulo 01246903,Brazil.
authors: Taila
authors: T
authors: Tuma
authors: Department of Pathology, University of Sao Paulo, Sao Paulo 01246903,Brazil.
authors: Alexandre
authors: A
authors: Fabro
authors: Pulmonary Division, Heart Institute Clinics Hospital, University of Sao Paulo, Sao Paulo 01246903, Brazil.
authors: Milena
authors: M
authors: Acencio
authors: Pulmonary Division, Heart Institute Clinics Hospital, University of Sao Paulo, Sao Paulo 01246903, Brazil.
authors: Ricardo
authors: R
authors: Terra
authors: Department of Pathology, University of Sao Paulo, Sao Paulo 01246903,Brazil.
authors: Edwin
authors: E
authors: Parra
authors: Pulmonary Division, Heart Institute Clinics Hospital, University of Sao Paulo, Sao Paulo 01246903, Brazil.
authors: Francisco
authors: F
authors: Vargas
authors: Pulmonary Division, Heart Institute Clinics Hospital, University of Sao Paulo, Sao Paulo 01246903, Brazil.
authors: Teresa
authors: T
authors: Takagaki
authors: Department of Pathology, University of Sao Paulo, Sao Paulo 01246903,Brazil vcapelozzi@lim05.fm.usp.br.
authors: Vera
authors: V
authors: Capelozzi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001699:Biometry; D017024:Chemotherapy, Adjuvant; D003701:Delta Sleep-Inducing Peptide / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis*; D051796:Inhibitor of Differentiation Proteins / Q000032:analysis*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000473:pathology; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C075640:ID3 protein, human; C039556:delta sleep-inducing peptide, N-Tyr-; D003701:Delta Sleep-Inducing Peptide
keywords: Lung adenocarcinoma; angiogenesis; immunohistochemistry; inhibitors of DNA binding/inhibitors of differentiation; morphometry; prognosis