Use of Immunostaining for the Diagnosis of Lymphovascular Invasion in Superficial Barrett's Esophageal Adenocarcinoma

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2020 Jun 7

PMID 32503448

Citations 2

Authors

Isao Hosono

Ryoji Miyahara

Kazuhiro Furukawa

Kohei Funasaka

Tsunaki Sawada

Keiko Maeda

Takeshi Yamamura

Takuya Ishikawa

Eizaburo Ohno

Masanao Nakamura

Hiroki Kawashima

Takio Yokoi

Tetsuya Tsukamoto

Yoshiki Hirooka

Mitsuhiro Fujishiro

Affiliations

Soon will be listed here.

Abstract

Background: The prevalence of Barrett's esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA.

Methods: We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2-40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment.

Results: H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2-40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively.

Conclusions: Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.

Citing Articles

The role of vascular invasion and lymphatic invasion in predicting recurrent thoracic oesophageal squamous cell carcinoma.

Ma Y, Yao X, Li Z, Chen J, Li W, Wang H World J Surg Oncol. 2022; 20(1):12.

PMID: 35012555 PMC: 8744266. DOI: 10.1186/s12957-021-02458-1.

Lymphovascular invasion quantification could improve risk prediction of lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma.

van de Ven S, Suzuki L, Gotink A, Ten Kate F, Nieboer D, Weusten B United European Gastroenterol J. 2021; 9(9):1066-1073.

PMID: 34609076 PMC: 8598963. DOI: 10.1002/ueg2.12151.

References

Kahn H, Bailey D, Marks A . Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Mod Pathol. 2002; 15(4):434-40. DOI: 10.1038/modpathol.3880543. View

Kozlowski M, Naumnik W, Niklinski J, Milewski R, Lapuc G, Laudanski J . Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer. Folia Histochem Cytobiol. 2011; 49(1):90-7. DOI: 10.5603/fhc.2011.0013. View

Weber S, Sauerwald A, Polcher M, Braun M, Debald M, Serce N . Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer. Int J Gynecol Cancer. 2012; 22(8):1442-8. DOI: 10.1097/IGC.0b013e318269139b. View

Eisen G, Sandler R, Murray S, Gottfried M . The relationship between gastroesophageal reflux disease and its complications with Barrett's esophagus. Am J Gastroenterol. 1997; 92(1):27-31. View

Everhart J, Ruhl C . Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases. Gastroenterology. 2009; 136(2):376-86. DOI: 10.1053/j.gastro.2008.12.015. View

Ishihara R, Oyama T, Abe S, Takahashi H, Ono H, Fujisaki J . Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population. J Gastroenterol. 2016; 52(7):800-808. DOI: 10.1007/s00535-016-1275-0. View

Gillison E, Powell J, McConkey C, Spychal R . Surgical workload and outcome after resection for carcinoma of the oesophagus and cardia. Br J Surg. 2002; 89(3):344-8. DOI: 10.1046/j.0007-1323.2001.02015.x. View

Tachimori Y, Ozawa S, Numasaki H, Fujishiro M, Matsubara H, Oyama T . Comprehensive Registry of Esophageal Cancer in Japan, 2009. Esophagus. 2016; 13:110-137. PMC: 4824839. DOI: 10.1007/s10388-016-0531-y. View

. Japanese Classification of Esophageal Cancer, 11th Edition: part I. Esophagus. 2017; 14(1):1-36. PMC: 5222932. DOI: 10.1007/s10388-016-0551-7. View

10.

Fujiwara Y, Arakawa T . Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009; 44(6):518-34. DOI: 10.1007/s00535-009-0047-5. View

11.

Estrella J, Hofstetter W, Correa A, Swisher S, Ajani J, Lee J . Duplicated muscularis mucosae invasion has similar risk of lymph node metastasis and recurrence-free survival as intramucosal esophageal adenocarcinoma. Am J Surg Pathol. 2011; 35(7):1045-53. DOI: 10.1097/PAS.0b013e318219ccef. View

12.

Kaiserling E . [Immunohistochemical identification of lymph vessels with D2-40 in diagnostic pathology]. Pathologe. 2004; 25(5):362-74. DOI: 10.1007/s00292-004-0693-6. View

13.

Koizumi S, Motoyama S, Iijima K . Is the incidence of esophageal adenocarcinoma increasing in Japan? Trends from the data of a hospital-based registration system in Akita Prefecture, Japan. J Gastroenterol. 2017; 53(7):827-833. DOI: 10.1007/s00535-017-1412-4. View

14.

Kojima M, Shimazaki H, Iwaya K, Kage M, Akiba J, Ohkura Y . Pathological diagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer: a framework for developing an objective pathological diagnostic system using the Delphi method, from the Pathology Working Group of the Japanese Society.... J Clin Pathol. 2013; 66(7):551-8. PMC: 3711366. DOI: 10.1136/jclinpath-2012-201076. View

15.

Raica M, Ribatti D . Targeting tumor lymphangiogenesis: an update. Curr Med Chem. 2010; 17(8):698-708. DOI: 10.2174/092986710790514471. View

16.

Shaheen N, Falk G, Iyer P, Gerson L . ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus. Am J Gastroenterol. 2015; 111(1):30-50. PMC: 10245082. DOI: 10.1038/ajg.2015.322. View

17.

Hewitt R, Powe D, Carter G, Turner D . Desmoplasia and its relevance to colorectal tumour invasion. Int J Cancer. 1993; 53(1):62-9. DOI: 10.1002/ijc.2910530113. View

18.

Fan L, Mac M, Frishberg D, Fan X, Dhall D, Balzer B . Interobserver and intraobserver variability in evaluating vascular invasion in hepatocellular carcinoma. J Gastroenterol Hepatol. 2010; 25(9):1556-61. DOI: 10.1111/j.1440-1746.2010.06304.x. View

19.

Harris E, Lewin D, Wang H, Lauwers G, Srivastava A, Shyr Y . Lymphovascular invasion in colorectal cancer: an interobserver variability study. Am J Surg Pathol. 2008; 32(12):1816-21. PMC: 2605104. DOI: 10.1097/PAS.0b013e3181816083. View

20.

Okamoto Y, Fujimori T, Ohkura Y, Sugai T, Arai T, Watanabe G . Histological assessment of intra- and inter-institutional reliabilities in detection of desmoplastic reaction in biopsy specimens of early colorectal carcinomas. Pathol Int. 2013; 63(11):539-45. DOI: 10.1111/pin.12110. View