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.
KeywordsColorectal cancer Pulmonary metastasis Pathology Necrosis
JS and GI contributed to the design and organization and conducted the study and wrote the manuscript. TS and HN helped in the immunohistochemical process and created the pathological database. MK, YO, MS, MF, TK, AO, and KS advised the direction of study and the interpretation of the data. KA, KT, TM, MI, and MT contributed to provide surgical samples and clinical data. All the authors reviewed and accepted the manuscript.
This work was supported in part by JSPS KAKENHI (16H05311).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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