Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p 5 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p 5 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the "colorectal continuum" concept.

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:awa LUniveritY. 13-1, Takara-machi, Kana:awa 920. Japan.Summarv To studv the effect of localised secretion of chemokines on tumour growth. the genes for human (hu interleukin 8 (IL-8). hu-MCP-1 (NICAF). hu-MIP-12 (LD78). murine (mu)-MCP-1 (JE). mu-MIP-lx or mu-MIP-2 A-ere introduced. v-ia mammalian expression vectors. into Chinese hamster ovarv (CHO) cells. and the abilitv of transfected cells to form tumours in vivo uas evaluated. The production of hu-IL-8. hu-MIP-lx or mu-MIP-lx bv transfected clones did not influence the growth rate in iitro. but drastically suppressed tumour growth A-hen injected subcutaneouslv (s.c.) into nude mice. However. clones transfected with hu-MCP-1. mu-NMCP-I or mu-MIP-2 did not shou-anv significant difference in growth rate in vivo compared u-ith clones transfected u-ith sector alone. Histological examination of the site of injection of CHO clones transfected w-ith hu-IL-8. hu-MIP-l1 or mu-MIP-lE showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activitv A-hen released. even at lou-doses. at the tumour site. A-hich mav be mediated by recruitment and targeting of neutrophilic granulocvtes to chemokinereleasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.

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It is highly possible that residual chordoma infiltrating the gluteal muscles accounts mainly for the local recurrences. Therefore, a precise preoperative assessment of the tumor infiltration into the gluteal muscles by magnetic resonance imaging is important for the prevention of local recurrence. For complete tumor removal, a radical wide posterior surgical margin of the gluteal muscles should be employed. A less radical anterior surgical margin is sufficient because there is a firm presacral fascia anterior to the sacrum. The appropriate surgical margin for the complete removal of the chordoma differs according to the location of the tumor and tissues involved.