Nuclear atypia grading score is a useful prognostic factor in papillary gastric adenocarcinoma Yuichiro Nakashima, 1,2 Takashi Yao, 3 Minako Hirahashi, 1 Shinichi Aishima, 1 Yoshihiro Kakeji, 2 Yoshihiko Maehara 2 & Masazumi Tsuneyoshi 1 1 Departments of Anatomic Pathology and 2 Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, and 3 Department of Human Pathology, Juntendo University School of Medicine, Tokyo Japan Date of submission 18 June 2010 Accepted for publication 24 December 2010 Nakashima Y, Yao T, Hirahashi M, Aishima S, Kakeji Y, Maehara Y & Tsuneyoshi M (2011) Histopathology 59, 841–849 Nuclear atypia grading score is a useful prognostic factor in papillary gastric adenocarcinoma Aims: To investigate nuclear atypical in papillary gastric adenocarcinoma (PGA). Method and results: Hundred cases of PGA were classified into two groups according to nuclear pleo- morphism and nuclear polarity; these groups were designated as high nuclear grade and low nuclear grade. Correlations between nuclear grade and clini- copathological features were evaluated for prognostic value. In order to evaluate which types of biological factors influence nuclear atypia, the expression of gastric-type mucin phenotype, p53, HER2 and Ki-67 detected by immunohistochemistry and DNA ploidy detected by laser scanning cytometry. The high nuclear grade group correlated with deeper wall invasion, the presence of lymphatic and venous invasion and the positivity of lymph node metastasis. High nuclear grade was an independent prognostic factor for disease-free survival. Moreover, significant correlations were ob- served between high nuclear grade and positivity of gastric-type mucin phenotype, p53 and HER2 and DNA aneuploidy. Conclusion: Nuclear grade could be a new and useful morphological predictor for high malignant potential in PGA. Keywords: DNA ploidy, human epidermal growth factor receptor 2 (HER2), nuclear atypia, p53, papillary gastric adenocarcinoma Abbreviations: HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; PGA, papillary gastric adenocarcinoma Introduction Papillary gastric adenocarcinoma (PGA) is one of the histological variants of gastric adenocarcinoma. PGA and tubular gastric adenocarcinoma have been inter- preted as belonging to the differentiated or intestinal type, whereas poorly differentiated adenocarcinoma and signet-ring cell carcinoma have been interpreted as being of the undifferentiated or diffuse type. Histopath- ologically, PGA is a well-differentiated exophytic carci- noma with elongated finger-like processes lined by cylindrical or cuboidal cells supported by fibrovascular connective tissue cores. Although PGA has been classified into differentiated-type gastric adenocarci- noma, as well as tubular adenocarcinoma, a subtype known for its low malignant potential, 1,2 the biological behaviour of PGA is characterized as having high malignant potential, a higher positive rate of liver metastasis 3 and lymph node metastasis 1,4,5 and poorer surgical outcome 1,3 compared with non-PGA carcino- mas. Several reports indicate that a group character- ized by high-grade malignancy exists within PGAs, distinguished by mucin expression of gastric adenocar- cinoma cells, 2,4,5 but its biological behaviour and prognostic significance remain unclear. Address for correspondence: T Yao, Department of Human Pathology, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. e-mail: tyao@juntendo.ac.jp Ó 2011 Blackwell Publishing Limited. Histopathology 2011, 59, 841–849. DOI: 10.1111/j.1365-2559.2011.04035.x