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. 2016 Nov 8;11(1):128.
doi: 10.1186/s13000-016-0580-5.

The clinicopathological significance of angiogenesis in hindgut neuroendocrine tumors obtained via an endoscopic procedure

Yoichiro Okubo  1 , Osamu Motohashi  2 , Norisuke Nakayama  2 , Ken Nishimura  2 , Rika Kasajima  3 , Yohei Miyagi  3 , Manabu Shiozawa  4 , Emi Yoshioka  5 , Masaki Suzuki  5 , Kota Washimi  5 , Kae Kawachi  5 , Madoka Nito  6 , Yoichi Kameda  5 , Tomoyuki Yokose  5
Affiliations

The clinicopathological significance of angiogenesis in hindgut neuroendocrine tumors obtained via an endoscopic procedure

Yoichiro Okubo et al. Diagn Pathol. .

Abstract

Background: As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors.

Methods: We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses.

Results: A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor.

Conclusions: Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.

Keywords: Angiogenesis; Hindgut; Microvessel; Neuroendocrine tumor.

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Figures

Fig. 1
Fig. 1
Representative histopathological findings of hindgut neuroendocrine tumors. Legend: a A photomicrograph showing a low-power field of a hindgut neuroendocrine tumor (NET), with evidence of invasion of the submucosal layer (hematoxylin and eosin (HE) staining; original magnification, ×20; scale bar represents 1000 μm). b A photomicrograph showing a high-power field of a hindgut NET. The tumor cells have a round-to-oval nucleus, and the nuclear atypia is relatively mild (HE staining; original magnification, ×400; scale bar represents 100 μm). c and d Among the 42 cases in our study, a positive immunoreactivity for synaptophysin was identified in 42 cases and for chromogranin A in 35 cases (immunohistochemistry, synaptophysin and chromogranin A; original magnification, ×100; scale bars represent 200 μm)
Fig. 2
Fig. 2
Representative images of venous and lymphatic invasion. Legend: a, b To determine the presence or absence of venous invasion, both EVG staining and immunohistochemistry for CD31 were performed. Venous invasion was confirmed, but no CD31-positive cells were identified. Such difficult cases were reviewed by more than two expert pathologists (EVG staining and immunohistochemistry for CD31; original magnification, ×200; scale bars represent 200 μm). c To determine the presence or absence of lymphatic invasion, immunohistochemistry for D2-40 was performed. Difficult cases were examined by more than two expert pathologists (Immunohistochemistry for D2-40; original magnification × 400; scale bar represents 100 μm)
Fig. 3
Fig. 3
Variation in microvessel density among tumors. Legend: a In this tumor, there are few CD31-positive endothelial cells and the tumor has an extremely low microvessel density. No venous invasion was observable (immunohistochemistry for CD31; original magnification, ×100, scale; bar represents 100 μm). b In this tumor, numerous CD31-positive endothelial cells were observable and the tumor has a high microvessel density. This is representative of most of cases with venous invasion (immunohistochemistry for CD31; original magnification, ×100; scale bar represents 100 μm)
Fig. 4
Fig. 4
Differences in microvessel density in tumors with and with without venous invasion. Legend: The microvessel density values of tumors with venous invasion were significantly higher than for tumors without venous invasion (*, p < 0.001, Mann–Whitney U test; values are expressed as the mean ± standard deviation)
Fig. 5
Fig. 5
Differences in lymphatic microvessel density in tumors with and without lymphatic invasion. Legend: The lymphatic microvessel density values of tumors with lymphatic invasion were significantly higher than for tumors without lymphatic invasion (*, p < 0.001, Mann–Whitney U test; values are expressed as the mean ± standard deviation)
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References

    1. Cho MY, Kim JM, Sohn JH, Kim MJ, Kim KM, Kim WH, Kim H, Kook MC, Park Do Y, Lee JH, Chang H, Jung ES, Kim HK, Jin SY, Choi JH, Gu MJ, Kim S, Kang MS, Cho CH, Park MI, Kang YK, Kim YW, Yoon SO, Bae HI, Joo M, Moon WS, Kang DY, Chang SJ. Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000–2009: Multicenter Study. Cancer Res Treat. 2012;44:157–65. doi: 10.4143/crt.2012.44.3.157. - DOI - PMC - PubMed
    1. Palmieri F, Brunocilla E, Bertaccini A, Guidi M, Pernetti R, Morselli-Labate AM, Martorana G. Prognostic value of lymphovascular invasion in bladder cancer in patients treated with radical cystectomy. Anticancer Res. 2010;30:2973–6. - PubMed
    1. Schoppmann SF, Bayer G, Aumayr K, Taucher S, Geleff S, Rudas M, Kubista E, Hausmaninger H, Samonigg H, Gnant M, Jakesz R, Horvat R. Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann. Surg. 2004;240:306–12. doi: 10.1097/01.sla.0000133355.48672.22. - DOI - PMC - PubMed
    1. Nakamura K, Osada M, Goto A, Iwasa T, Takahashi S, Takizawa N, Akahoshi K, Ochiai T, Nakamura N, Akiho H, Itaba S, Harada N, Iju M, Tanaka M, Kubo H, Somada S, Ihara E, Oda Y, Ito T, Takayanagi R. Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification. Scand. J. Gastroenterol. 2016;51:448–55. doi: 10.3109/00365521.2015.1107752. - DOI - PubMed
    1. Stinner B, Rothmund M. Neuroendocrine tumours (carcinoids) of the appendix. Best Pract. Res. Clin. Gastroenterol. 2005;19:729–38. doi: 10.1016/j.bpg.2005.06.003. - DOI - PubMed

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