Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa.

We examined the relationship between vascular endothelial growth factor (VEGF)-C expression and lymph node metastases in gastric carcinomas invading the submucosa. Of the six human gastric carcinoma cell lines, two constitutively expressed VEGF-C mRNA. In three of 12 gastric biopsy specimens (25%), VEGF-C mRNA was detected in tumour tissues, but not in corresponding normal mucosa by reverse transcriptase-polymerase chain reaction (RT-PCR). Of the 139 resected gastric carcinomas, 44 (32%) showed intense cytoplasmic VEGF-C immunoreactivity in many cancer cells at the invading edge. VEGF-C immunoreactivity was associated with greater depth of tumour invasion, lymphatic invasion and lymph node metastases. In addition, vessel count was also significantly higher in the VEGF-C immunoreactive tumours than in other tumours. These results suggest that VEGF-C may be involved in the progression of human gastric carcinoma, particularly via lymphangiogenesis. VEGF-C expression at the invading edge of a gastric carcinoma may be a sensitive marker for metastasis to the lymph nodes.

Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas.

The purpose of this study was to investigate the expression of vascular endothelial growth factor (VEGF) -C in human esophageal squamous cell carcinomas to elucidate its role in lymph node metastasis and tumor progression. The expression of VEGF-C and flt-4 genes was examined in 5 esophageal carcinoma cell lines, 12 fresh biopsy specimens and 48 archival surgical specimens of human esophageal carcinoma tissues by RT-PCR and immunohistochemistry. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was also carried out and microvessels were quantified by counting vessels in a 200x field in the most vascular area of the tumor. Of the 5 human esophageal carcinoma cell lines, 4 constitutively expressed VEGF-C mRNA. In 8 (66.7%) of 12 cases, VEGF-C mRNA was detected in only tumor tissues but not in normal mucosa by RT-PCR. There was a significant relationship between VEGF-C and flt-4 mRNA expression. Out of the 48 surgical specimens of esophageal carcinomas, 19 (39.6%) and 10 (20.8%) exhibited intense VEGF-C immunoreactivity in the cytoplasm of many cancer cells and the stromal cells, respectively. In contrast, Flt-4 was mainly expressed on the lymphatic endothelial cells. Normal and dysplastic esophageal squamous epithelium exhibited no or faint cytoplasmic staining of VEGF-C. VEGF-C expression correlated with depth of tumor invasion, tumor stage, venous invasion, lymphatic invasion and lymph node metastasis. Vessel count was significantly higher in the VEGF-C positive tumors than in the negative tumors. These results overall suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and angiogenesis in human esophageal carcinoma.

Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion.

The deepest invasive portion of colorectal carcinoma (CRC) is considered to be the part, which ultimately will invade, spread locally and give metastasis. We have previously reported that histologic differentiation at the deepest invasive portion of CRC closely correlate with metastatic potential and is useful in understanding the curability of endoscopic mucosal resection (EMR). The aim of this study is to clarify the conditions of curative EMR for CRC with submucosally (sm) massive invasion. A total of 521 cases with sm invasive CRC (Group A, 470 surgically resected cases; Group B, 51 followed-up cases after EMR) were studied. The depth of sm invasion was defined as the practically measured distance from muscularis mucosae. Histologic subclassification was performed at the deepest invasive tumor margin as: well-differentiated (W), moderately differentiated (M) and poorly differentiated (Por). By assessing glandular configuration and cellular arrangement, M type was further subdivided into two different groups; moderately-well differentiated (Mw) and moderately-poorly differentiated (Mp). In group A, lymph node (LN) metastasis was detected in 45 (9.6%) of 470 cases. W or Mw lesions showed LN metastasis in 4.9% (19/388). Mp or Por lesions showed LN metastasis in 37.3% (25/67) (W/Mw vs Mp/Por; p<0.01). Of 45 cases with LN metastasis that could be measured the practical distance of sm invasion, W or Mw lesions showed no LN metastasis in cases within 1,500 micrometer invasion. However, Mp or Por lesions showed LN metastasis in cases within 1,500 micrometer invasion (5/15, 33.3%, minimum 400 micrometer invasion; so-called scanty invasion). In group B, none of 51 cases died of LN metastasis and showed no other metastasis, although 17 cases (33.3%) showed an sm invasion more than 1,500 micrometer. These results indicated that CRC even with sm massive invasion can be cured by complete EMR on conditions that the depth of sm invasion is within 1,500 micrometer and histologic grade at the deepest invasive portion is W or Mw, if there are no vessel involvement. However, cases with Mp or Por grade were not curative by EMR, even if they showed an sm scanty invasion.