Clinicopathological characteristics associated with necrosis in pulmonary metastases from colorectal cancer

Metastatic lung cancers from the colon and rectum (MLCR) frequently have necrotic components. The aim of this study is to elucidate clinicopathological factors associated with the amount of necrosis in MLCR. Ninety patients who underwent the first pulmonary metastasectomy for MLCR with a tumor diameter ≦ 3.0 cm and without chemotherapy were enrolled in this study. Analyzing digitally scanned pathological slides, we calculated the necrosis percentage (NP, the necrosis area divided by the tumor area). The relationship between NP and clinicopathological factors was analyzed. Moreover, to determine whether NP was affected by tissue hypoxia, vascularization, or tumor cell proliferation, tissues were analyzed by immunohistochemical staining using carbonic anhydrase IX (CAIX), CD34 antibodies, and Ki-67 antibodies, respectively. Median tumor area and NP were 0.69 cm² (0.11-3.01) and 13.1% (0-71.6), respectively. Although NP was not associated with the tumor area, it was significantly higher in the patients with a positive smoking history (8.14% vs 17.1%, p = 0.045). Other clinicopathological factors were not correlated with NP. Immunohistochemical analysis revealed that CA IX expression on tumor cells, CD34 micro-vessel density, CD34 micro-vessel area, and Ki-67 index were not significantly associated with NP. NP in the primary site was not associated with NP in the pulmonary metastasis. NP was not determined by tumor size, tissue hypoxia, vascularization, or tumor cell proliferation. Positive correlation of NP with smoking history suggests a unique lung microenvironment in smokers which makes necrosis of MLCR more likely to occur.