ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion
0
조회
0
다운로드
3
인용
0
참고문헌
초록
Background: ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis. Methods: Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics. Results: The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%). Conclusions: The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.
Abstract
Background: ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis. Methods: Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics. Results: The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%). Conclusions: The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.
참고문헌 (28)
- Knudsen JB, "Venous and nerve invasion as prognostic factors in postoperative survival of patients with resectable cancer of the rectum", Dis Colon Rectum, 26, pp.613~617 (1983)
- Cheng L, "Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma", J Urol, 174, pp.2181~2185 (2005)
- Manoharan M, "Lymphovascular invasion in radical cystectomy specimen: is it an independent prognostic factor in patients without lymph node metastases?", World J Urol, 28, pp.233~237 (2010)
- Guntupalli SR, "Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer", Gynecol Oncol, 124, pp.31~35 (2012)
- Hassell L, "Electronic capture and communication of synoptic cancer data elements from pathology reports: results of the Reporting Pathology Protocols 2 (RPP2) project", J Registry Manag, 36, pp.117~124 (2009)
- Compton CC, "Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999", Arch Pathol Lab Med, 124, pp.979~994 (2000)
- Harris EI, "Lymphovascular invasion in colorectal cancer: an interobserver variability study", Am J Surg Pathol, 32, pp.1816~1821 (2008)
- Kryvenko ON, "Histologic criteria and pitfalls in the diagnosis of lymphovascular invasion in radical prostatectomy specimens", Am J Surg Pathol, 36, pp.1865~1873 (2012)
- Kirsch R, "Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists", Am J Surg Pathol, 37, pp.200~210 (2013)
- Lim CS, "Clinical value of immunohistochemically detected lymphovascular space invasion in early stage cervical carcinoma", Ann Surg Oncol, 15, pp.2581~2588 (2008)
- O’Donnell RK, "Immunohistochemical method identifies lymphovascular invasion in a majority of oral squamous cell carcinomas and discriminates between blood and lymphatic vessel invasion", J Histochem Cytochem, 56, pp.803~810 (2008)
- Miettinen M, "ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma", Am J Surg Pathol, 35, pp.432~441 (2011)
- Birdsey GM, "Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin", Blood, 111, pp.3498~3506 (2008)
- Landis JR, "The measurement of observer agreement for categorical data", Biometrics, 33, pp.159~174 (1977)
- Branchereau J, "Prognostic value of the lymphovascular invasion in high-grade stage pT1 bladder cancer", Clin Genitourin Cancer, 11, pp.182~188 (2013)
- Weber SK, "Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer", Int J Gynecol Cancer, 22, pp.1442~1448 (2012)
- Belsante M, "Lymphovascular invasion in clear cell renal cell carcinoma: association with disease-free and cancer-specific survival", Urol Oncol (2013)
- Matsuo K, "Significance of lymphovascular space invasion in epithelial ovarian cancer", Cancer Med, 1, pp.156~164 (2012)
- Massabeau C, "The prognostic significance of lymphovascular invasion on biopsy specimens in lung cancer treated with definitive chemoradiotherapy", Clin Lung Cancer, 13, pp.59~67 (2012)
- Rami-Porta R, "Adjuvant therapy for resected non-small-cell lung cancer with lymphovascular invasion", J Thorac Oncol, 8, pp.9~10 (2013)
- Edge SB, "AJCC cancer staging manual" (2010), Springer
- Epstein JI, "Recommendations for the reporting of prostate carcinoma: Association of Directors of Anatomic and Surgical Pathology", Am J Clin Pathol, 129, pp.24~30 (2008)
- Suzuki H, "Nuclear β-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma", Anticancer Res, 28, pp.1821~1830 (2008)
- Ishibashi K, "Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer", Tech Coloproctol, 17, pp.51~57 (2013)
- Seo SI, "Comparison of recurrence patterns between ≤5 years and >5 years after curative operations in colorectal cancer patients", J Surg Oncol, 108, pp.9~13 (2013)
- Dobbins WO 3rd, "The intestinal mucosal lymphatic in man. A light and electron microscopic study", Gastroenterology, 51, pp.994~1003 (1966)
- Fenoglio CM, Kaye GI, Lane N. Distribution of human colonic lymphatics in normal, hyperplastic, and adenomatous tissue. Its relationship to metastasis from small carcinomas in pedunculated adenomas, "Distribution of human colonic lymphatics in normal, hyperplastic, and adenomatous tissue. Its relationship to metastasis from small carcinomas in pedunculated adenomas, with two case reports", Gastroenterology, 64, pp.51~66 (1973)
- Kenney BC, "Identification of lymphatics within the colonic lamina propria in inflammation and neoplasia using the monoclonal antibody D2-40", Yale J Biol Med, 81, pp.103~113 (2008)