Intratumoral lymphatic vessel density in vulvar squamous cell carcinomas: a possible association with favorable prognosis.

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

Intratumoral lymphatic vessel density and clinicopathologic features of patients with early-stage cervical cancer after radical hysterectomy.

INTRODUCTION: Lymphangiogenesis plays a key role in tumor growth, progression, and metastasis, yet few studies have investigated lymphatic vessel density (LVD) in cases of cervical cancer. The aim of this retrospective study was to evaluate intratumoral LVD, in addition to other histologic variables, in relation to lymph node metastases and survival of patients with stage IB to IIA cervical cancer after radical hysterectomy. METHODS: Between 2000 and 2008, 144 patients had a diagnosis of cervical uterine cancer and underwent radical hysterectomy. Tumor stages for these patients were identified according to the criteria of the International Federation of Gynecology and Obstetrics and included 84 stage IB1, 44 stage IB2, and 16 stage IIA cases. With an antibody directed against human podoplanin (D2-40), immunohistochemical staining was used to measure LVD. The correlation between LVD and clinicopathologic features of the resected tumors was analyzed. RESULTS: Lymphatic vessel density was significantly higher in tumors less than 2 cm in diameter (P = 0.001) and in tumors with 1.0-cm-or-less depth of invasion (P = 0.007), with early stage (P = 0.001), and with negative lymph nodes (P = 0.05). After multivariate analysis, the predictive factors associated with lymph node metastases were depth of infiltration (P = 0.027), lymphovascular space invasion (P < 0.001), and parametrial involvement (P = 0.01). For patient death, the predictive factors were International Federation of Gynecology and Obstetrics stage (P = 0.017), histologic type (P = 0.010), lymph node status (P = 0.031), and histologic grade (P = 0.041). Lymphatic vessel density was not a predictive variable for lymph node metastasis or death. CONCLUSIONS: Intratumoral LVD was greater in early cervical cancer (ie, smaller tumors, early clinical stage, and negative lymph nodes), and no relationship between LVD and lymph node metastases or survival was observed.

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas.

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6 percent) cases, with 29/31 (93.5 percent) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9 percent vs. 22.6 percent, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5 percent vs. 21.6 percent, respectively. In 27/143 (18.8 percent) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5 percent vs. 3.7 percent, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.