Histopathologic determinants of regional lymph node metastasis in early colorectal cancer

Abstract

BACKGROUND. Early colorectal cancer (ECC) is curable by endoscopic local resection; however, 10% of patients with ECC exhibit lymph node (LN) metastasis. In the current study, accurate predictors for LN metastasis in patients with ECC were examined by using immunohistochemistry with the lymphatic endothelial hyaluronan receptor 1 (LYVE‐1) antibody to discriminate between lymphatics and blood vessels. METHODS. Colorectal tissue specimens obtained from 71 patients with ECC, including 28 patients with regional LN metastasis, were immunostained with antibodies against LYVE‐1, β‐catenin, claudin‐3, claudin‐4, and cytokeratin. The significance of the histopathologic variables for LN metastasis in ECC was investigated on the basis of specific histopathologic parameters. RESULTS. Lymphatic invasion confirmed by LYVE‐1 immunohistochemistry was observed mainly in the submucosal area around the primary tumor and rarely was observed in the tumor. Expression patterns of β‐catenin, claudin‐3, and claudin‐4 in cancer cells at the invasive front were irrelevant to LN status. Tumor size, depth of invasion, histologic tumor type, budding formation, and lymphatic invasion were statistically significant to LN status in univariate analysis; however, only 2 factors—lymphatic invasion and budding formation at the invasive front—were independent predictors of LN metastasis in ECC. CONCLUSIONS. LYVE‐1 immunohistochemistry appeared to be a useful method for detecting lymphatics invaded by cancer cells, and detailed examination of the submucosa around the tumor may be important for predicting LN metastasis. When lymphatic invasion and budding formation are observed histopathologically in patients with ECC, additional therapy, such as adjuvant chemotherapy or a curative resection of the regional LN, may be required. Cancer 2008. © 2008 American Cancer Society.

Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer

“…Previous studies using different scoring systems such as those proposed by Hase, Nakamura, Ueno and Wang [7][8][9][10][11][12][13][14][15][16][17] have demonstrated that tumor budding is a strong independent prognostic parameter; however, the implementation of these results in clinical practice is hampered by the lack of a standardized scoring system. In a previous study by our group, after comparison of the several existing scoring methods, the 1 HPF and 10 HPFs approaches came out as the most reliable and reproducible methods of assessing tumor budding.…”

“…[7][8][9][10][11][12][13][14] Moreover, tumor budding has repeatedly been linked to unfavorable disease outcome and has been shown to have an independent adverse effect on disease-free and overall survival. [1][2][3][4][5][6][7][8][9][10][11][12][13] Although tumor budding has been recognized by the International Union for Cancer Control as an additional prognostic factor in colorectal cancer, it remains largely unreported in daily diagnostic work. In contrast to other cancers, including breast and prostate cancer where scores are used in daily routine, there has not been real progress with respect to additional prognostic factors or scoring systems in colorectal cancer.…”

Tumor budding in colorectal carcinoma: time to take notice

“…16,19,22,25,26,29,30,37,43,44 In the largest of these studies, Ueno et al 26 demonstrated that, in submucosally invasive colorectal carcinoma, high tumor grade, lymphovascular invasion, and tumor budding are the three factors independently associated with lymph node metastases. Patients without any of these three features showed exceptionally low rates of lymph node metastases (1%, 1/138); in the presence of one risk factor, the rate of nodal metastases increased substantially to 21% (12/58), and when two or three factors were present, the risk was 36% (20/55), suggesting that in the absence of these factors, polypectomy alone is sufficient treatment for early colorectal carcinoma provided the resection margins are clear.…”

“…12,13,22,23,31,32,38,40,43,44,48,51,54,55 The use of immunohistochemistry in the assessment of budding is somewhat controversial: some authors argue that the evaluation of budding should be limited to H&E-stained slides because of the cost and impracticality of performing immunohistochemistry in routine cases, while others argue that immunohistochemistry should be used routinely to improve the accuracy and reproducibility of bud counts. In addition to cost considerations, the use of immunohistochemistry may also require the establishment of a separate cutoff for defining positive budding.…”

Invasive front of colorectal cancer: Dynamic interface ofpro-/anti-tumor factors

“…A significant association between tumor budding and lymph node positivity has been consistently demonstrated correlating with tumor aggressiveness and more advanced TNM stage [32][33][34][35][36][37][38][39][40][41][42][43] . Tumor budding is frequently associated with poorly differentiated tumors, and with the presence of vascular and lymphatic invasion independently of disease extent [44][45][46][47][48] .…”