Abstract
The present study aimed to elucidate the clinicopathological significance and prognostic implications of tumor–stroma ratio (TSR) in colorectal cancers (CRCs). TSRs were investigated in 266 human CRC specimens. The correlations between TSR and clinicopathological characteristics and survival were evaluated. The hypoxia-inducible factor-1α (HIF-1α) immunohistochemical expression of tumor cells and microvessel density (MVD) of stroma were compared between stroma-low and stroma-high subgroups. Results: Stroma-low was found in 185 of 266 CRCs (69.5%). Stroma-low was significantly correlated with less frequent vascular and perineural invasion and distant metastasis than stroma-high. HIF-1α of tumor cells was more highly expressed in the stroma-high subgroup than in the stroma-low subgroup. In addition, MVD was significantly higher in the stroma-high subgroup compared to the stroma-low subgroup. The stroma-low rate was increased considerably in CRCs with a mucinous component and decreased in CRCs with a micropapillary component. There were significant correlations between stroma-low and better overall and recurrence-free survivals. Similar to the literature, we observed that stroma-low was significantly correlated with favorable tumor behaviors and better survival. The microscopic examination of TSR can be useful for predicting the prognosis of CRC patients.
Highlights
Epithelial malignant tumors initially invade the basement membrane and sequentially progress to the stroma
We prepared glass slides with hematoxylin and eosin (H&E) staining from the formalinfixed paraffin-embedded section to evaluate the tumor–stroma ratio (TSR)
Because the amount of stroma can be different within the tumor, all H&E slides were screened and evaluated for TSR
Summary
Epithelial malignant tumors initially invade the basement membrane and sequentially progress to the stroma. The interaction between the tumor cells and stroma, including the extracellular matrix, is important in the tumor progression of many cancers [1]. The prognostic role of tumor-infiltrating lymphocytes and the immunoscore has been reported in CRC [7,8]. These results suggest the crucial roles of intratumoral stroma in CRC. We performed a subgroup analysis based on cutoffs of TSR and histologic subtypes. Since the tumor progression requires angiogenesis in the stroma, we compared the angiogenesis between stroma-low and stroma-high subgroups with the HIF-1α expression of tumor cells and MVD of the stroma
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