Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas.

Although vascular invasion (VI) is recognized as an important predictor of lymph node metastasis and a significant prognostic factor in head and neck squamous cell carcinoma (HNSCC), there is currently no common definition for the pathological evaluation of VI status. We reviewed the medical records of 63 consecutive resected primary oral tongue SCCs (OTSCCs) without preoperative treatment between June 1999 and April 2008, and evaluated VI status by investigating lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) by using immunohistochemistry (IHC) with monoclonal antibody D2-40 (D2-40) and Elastica van Gieson (EVG) staining, respectively. Subsequently, we analyzed their correlations with cervical lymph node metastasis and prognosis. LVI was found in 16 of the 63 tumors (25.4%) and BVI was in 32 tumors (50.8%). Univariate analysis revealed that the presence of LVI is statistically correlated with lymph node metastasis. Moreover, multivariate logistic regression analysis revealed that LVI is an independent risk factor of nodal metastasis (odds ratio=4.262, 95% confidence interval=1.262-14.397, p=0.020). In contrast, Kaplan-Meier survival analysis revealed that patients with BVI had a significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those without BVI (68.6% versus 90.3%, p=0.028 and 68.6% versus 93.5%, p=0.013, respectively). The present study clearly demonstrated that LVI at primary OTSCC had significant correlation with lymph node metastasis, and that BVI was significantly associated with recurrence and poor prognosis. Evaluation of VI status, as LVI and BVI status separately, using IHC with D2-40 and EVG staining may be useful in predicting lymph node metastasis and poor prognosis in OTSCCs.

Michikawa C ，Uzawa N ，Kayamori K ，Sonoda I ，Ohyama Y ，Okada N ，Yamaguchi A ，Amagasa T ... -  《-》

Significant effects of lymph and blood vascular invasion on the prognosis of early-stage cervical squamous cell carcinoma.

In the past 10 years, therapeutic advances have led to improved short-term efficacy for cervical carcinoma; however, the 5-year survival rate was not significantly enhanced. To investigate the effects of blood vessel invasion (BVI) and lymph vessel invasion (LVI) on the prognosis of early-stage cervical squamous carcinoma, we carried out immunohistochemical staining to distinguish blood and lymph vessels. Specimens from 111 IB-stage or IIA-stage cervical squamous carcinoma cases were examined for BVI and LVI by streptavidin-peroxidase immunohistochemistry using CD-34 and D2-40 monoclonal antibodies. Data were analyzed with SPSS version 13.0 (SPSS, Chicago, IL, USA) statistical software. The survival rate and survival curve were derived by using the life table method and the Kaplan-Meier method, respectively. Multivariate prognosis analysis was conducted with Cox regression model, and prognosis was evaluated by measuring overall survival (OS) and progression-free survival (PFS). BVI/LVI double positivity was an independent prognostic factor for both OS and PFS, whereas lymph node metastasis and surgical margin positivity affected only PFS. Patients inflicted with either BVI or LVI displayed no significant difference in survival time. Lymph-vascular space invasion (LVSI), referring to blood and/or lymph vessel invasion correlated with lymph node metastasis, surgical margin positivity, depth of cervical interstitial invasion, squamous cell carcinoma antigen (SccAg) and age. LVSI was a risk factor for both recurrence (P = 0.013, relative risk 3.060) and death (P = 0.005, relative risk 4.512). Post-operation auxiliary external radiation did not improve survival for LVSI-positive cases. BVI/LVI double positivity constitutes an independent prognostic factor for early-stage cervical squamous carcinoma.

Zhang Y ，Yan M ，He J ，Sun J ，Sun X ... -  《-》

A multivariate analysis of blood vessel and lymph vessel invasion as predictors of ovarian and lymph node metastases in patients with cervical carcinoma.

To the authors' knowledge there are few available data regarding the influence of lymphovascular space invasion, which has been examined separately as two components (lymphatic vessel invasion [LVI] and blood vessel invasion [BVI]), in the metastasis of cervical carcinoma. LVI and BVI, which include capillary vessel invasion, were reviewed retrospectively based on the histopathologic slides of 239 women with cervical carcinoma who were treated with radical hysterectomy. The correlation between lymph node and/or ovarian metastases and LVI, BVI, and other histopathologic factors was investigated by multiple logistic regression analysis. The influence of LVI and BVI on survival was examined by Cox regression analysis. The rate of incidence of LVI was higher than that of BVI in all stages of cervical carcinoma (P < 0.0001 for International Federation of Gynecology and Obstetrics Stage IB and Stage II disease and P < 0.05 for Stage III disease). The incidence rate of BVI increased as LVI became more prominent and there was a significant correlation between the two findings (P < 0.0001). BVI was more frequent in adenocarcinoma/adenosquamous carcinoma than in squamous cell carcinoma (P < 0.05). LVI (P < 0.0001) and parametrial invasion (P < 0.0001) were significantly related to lymph node metastasis on multivariate analysis. Conversely, BVI (P < 0.05) and parametrial invasion (P < 0.0025), as well as adenocarcinoma or adenosquamous carcinoma (P < 0.0005), were significantly related to ovarian metastasis on multivariate analysis. With regard to the prognostic significance of these components, it was found that BVI (hazards ratio [HR] = 2.0), ovarian metastasis (HR = 6.5), and lymph node metastasis (HR = 5.5) were significantly related to a poor prognosis in women with cervical carcinoma. Ovarian metastasis may occur via hematogenous spread of cervical carcinoma. The results of the current study suggest that BVI, including capillary vessels, that is diagnosed separately from LVI using hematoxylin and eosin stained sections may be an important prognostic factor for patients with cervical carcinoma.

Sakuragi N ，Takeda N ，Hareyama H ，Fujimoto T ，Todo Y ，Okamoto K ，Takeda M ，Wada Si ，Yamamoto R ，Fujimoto S ... -  《CANCER》

Prognostic significance of immunohistochemically detected blood and lymphatic vessel invasion in colorectal carcinoma: its impact on prognosis.

Liang P ，Nakada I ，Hong JW ，Tabuchi T ，Motohashi G ，Takemura A ，Nakachi T ，Kasuga T ，Tabuchi T ... -  《ANNALS OF SURGICAL ONCOLOGY》

Lymphatic vessel invasion detected by the D2-40 monoclonal antibody is an independent prognostic factor in node-negative esophageal squamous cell carcinoma.

D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC). A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated. An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P < 0.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P = 0.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P = 0.048). LVI detected by D2-40 staining was an independent prognostic factor in patients with node-negative ESCC.

Imamura Y ，Watanabe M ，Nagai Y ，Baba Y ，Hirashima K ，Karashima R ，Iwatsuki M ，Yoshida N ，Kinoshita K ，Kurashige J ，Iyama K ，Baba H ... -  《-》