Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma

• Published in: Modern pathology Vol. 21; no. 8; pp. 992 - 1001
• Main Authors: Kamiya, Kazunori, Hayashi, Yuichiro, Douguchi, Junya, Hashiguchi, Akinori, Yamada, Taketo, Izumi, Yotaro, Watanabe, Masazumi, Kawamura, Masafumi, Horinouchi, Hirohisa, Shimada, Naoki, Kobayashi, Koichi, Sakamoto, Michiie
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.08.2008; Nature Publishing Group US; Elsevier Limited
• Subjects: Adenocarcinoma, Papillary - chemistry; Adenocarcinoma, Papillary - mortality; Adenocarcinoma, Papillary - pathology; Adult; Aged; Aged, 80 and over; Basement Membrane - ultrastructure; beta Catenin - analysis; Biomarkers, Tumor - analysis; Cadherins - analysis; Connective tissue; Disease-Free Survival; electron microscopy; Female; Health care; Histopathology; Humans; Immunoenzyme Techniques; immunohistochemistry; Ki-67 Antigen - analysis; Laboratory Medicine; Laminin - analysis; lung adenocarcinoma; Lung cancer; Lung Neoplasms - chemistry; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymph Nodes - pathology; Lymphatic system; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; micropapillary pattern; Microscopy; Middle Aged; Neoplasm Staging; original-article; Pathology; Patients; prognosis; Survival analysis; Survival Rate; Thoracic surgery; Japan; histopathology; micropapillary pattern; electron microscopy; immunohistochemistry; prognosis; lung adenocarcinoma
• ISSN: 0893-3952; 1530-0285; 1530-0285
• DOI: 10.1038/modpathol.2008.79

The micropapillary pattern is characterized by small papillary tufts with no fibrovascular core lying in spaces and has been reported as an aggressive variant of carcinoma in several organs. We investigated the histopathobiological properties of the micropapillary pattern with immunohistochemistry, serial sections, and electron microscopy in lung adenocarcinoma. We further analyzed its clinicopathological character and prognosis. The subjects included 383 adenocarcinoma cases, of which 184 (48%) were micropapillary pattern-positive and 199 (52%) were micropapillary pattern-negative. On histology, micropapillary tufts seemed to float in the alveolar space or spaces encased by connective tissues, whereas serial sections revealed that most tufts had continuity with other tufts and even with the main tumor. Positive staining for the adhesion molecules E-cadherin and Β-catenin suggested the preservation of tight adhesion, and electron microscopy showed the existence of intercellular junctions. Negative staining for laminin and loss of basement membrane as determined by electron microscopy suggest a loss of cell–matrix contact. Positive staining for Ki-67 indicates that cells constituting micropapillary tufts retained their proliferation potency. There were no CD34-positive cells in micropapillary tufts, and the loss of the vascular core was confirmed. In micropapillary pattern-positive cases, lymphatic invasion was identified significantly more frequently than in micropapillary pattern-negative cases (P<0.001), even at stageIA (without lymph node metastasis, N=197) (P<0.001). The 5-year and 10-year overall survival rates of the micropapillary pattern-positive stageIA group were 77.6 and 67.6%, respectively, which were significantly less than those of the micropapillary pattern-negative stageIA group (98.1 and 98.1%) (P=0.001). In conclusion, cells constituting the micropapillary pattern are likely to have acquired anchorage-independent growth and a potential for high malignancy.