title: Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma.
abstract: Histological vascular invasion (VI) by tumors is reportedly a risk factor influencing recurrence or survival after surgical treatment; however, few studies have evaluated which VI features affect recurrence or survival. The objective of this study was to evaluate how VI features affect recurrence in lung adenocarcinoma patients. We selected 106 patients with pathological stage I lung adenocarcinoma who showed VI and examined the properties of intravascular tumors associated with recurrence. First we investigated the relationship between the frequency of VI in a histological cross-section and the incidence of recurrence; however, a significant impact was not observed. Microscopic examination revealed the intravascular tumors were composed of not only cancer cells but also non-cancerous cells. To examine whether the characteristics of intravascular cancer cells and/or non-cancerous cells have prognostic value, we examined the expression levels of epithelial-mesenchymal transition-related markers in cancer cells and the numbers of infiltrating non-cancerous cells, including macrophages, endothelial cells, and fibroblasts. High levels of E-cadherin expression in the intravascular cancer cells were significant predictors of recurrence (P = 0.004), whereas the expressions of CD44, CD44 variant 6, and vimentin were not. Large numbers of intravascular CD204(+) macrophages (P = 0.016), CD34(+) microvessels (P = 0.007), and α-smooth muscle actin (+) fibroblasts (P = 0.033) were also significant predictors of recurrence. Our results indicated VI with abundant stromal cell infiltrates might be a predictor of recurrence and suggested the tumor microenvironment created by cancer cells and stromal cells within the blood vessel may play an important role during the metastatic process.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kaseda
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Keiju
authors.initials: K
authors.lastname: Aokage
authors.forename: Akiko
authors.initials: A
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.forename: Mitsutomo
authors.initials: M
authors.lastname: Kohno
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; D014746:Vimentin