Micropapillary lung adenocarcinoma: a distinctive histologic subtype with prognostic significance. Case series

Department of Pathology, Hospital General Universitary Gregrorio, Marañón, Spain.
Human Pathlogy (Impact Factor: 2.81). 04/2008; 39(3):324-30. DOI: 10.1016/j.humpath.2007.05.029
Source: PubMed

ABSTRACT The aims of the present work were to evaluate the prognostic significance of the micropapillary pattern of lung adenocarcinoma and determine whether there are differences in the behavior of this type of tumor according to its immunohistochemical profile. A series of 191 consecutively resected pulmonary adenocarcinomas were divided into those with (n = 62) and those without (n = 129) micropapillary components. The disease was stage I in 38 and 54 patients, respectively. The 5-year survival rates of patients with and without micropapillary components were 54% and 77%, respectively (log rank P = .03). In multivariate survival analysis, the micropapillary component proved to be an independent prognostic factor (hazard ratio, 3.2). Five autopsy cases were used to investigate the immunohistochemical profile. The percentages of cases positive for various markers were 56.7 for p53, 94 for Ki67, 85.1 for c-myc, 2.9 for Bcl-2, 35.8 for epidermal growth factor receptor, 43.3 for cyclin D1, and 46.3 for Bax. The prognostic value was evaluated according to the expression of the different markers in micropapillary carcinomas in stage I. In univariate analysis, only cyclin D1 expression and Bax expression were associated with significantly worse survival (log rank P = .03 and P = .02, respectively). We conclude that it is important to recognize the micropapillary growth pattern in lung adenocarcinoma. Moreover, cyclin D1 and Bax seem to be markers of a poor prognosis.

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    ABSTRACT: According to the International Multidisciplinary Classification of Lung Adenocarcinoma (LAD) by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) in 2011, the diagnosis of LAD is changing from simple morphology into a comprehensive multidisciplinary classification. The aim of this study is to detect the expression of Notch-1 and analyze its clinicopathological or prognostic significance in different histological subtypes of Lung Adenocarcinomas (LADs). Western blot and Semi-quantitative Reverse transcription-polymerase chain reaction (RT-PCR) assays, as well as immunohisitochemistry, were performed to detect the expression of Notch-1 in LAD cells and tissue samples. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the correlation of Notch-1 expression with clinicopathological factors and prognosis of LAD patients. The expression level of Notch-1 protein in LAD cell lines or tissues was significantly lower than that in normal human bronchial epithelial cell line (16HBE) or nontumor tissues (P < 0.05). By statistical analyses, it was observed that negative Notch-1 expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.026) in LAD patients. Also, the recurrence rate of Notch-1-positive group was higher than the Notch-1-negative group (P = 0.001), and patients with positive Notch-1 expression have a prolonged progression of overall survival (P = 0.033). More interestingly, the expression of Notch-1 protein was often observed to be negative in solid predominant adenocarcinoma (SPA) tissues, but highly expressed in papillary predominant adenocarcinoma (PPA) and micropapillary predominant adenocarcinoma (MPA) tissues. Kaplan-Meier survival analysis showed that patients with positive Notch-1 expression had a prolonged progression of overall survival compared with those with negative Notch-1 expression (P = 0.033). The median survival time of Notch-1-positive or negative patients was 64.6 months (95% CI: 31.497-97.703 months) or 36.0 months (95% CI: 12.132-59.868 months). Notch-1 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in LAD for diagnosis or prognosis.
    Journal of Experimental & Clinical Cancer Research 10/2013; 32(1):84. DOI:10.1186/1756-9966-32-84 · 3.27 Impact Factor
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    ABSTRACT: Background A new histological classification by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) for lung adenocarcinoma (LAC) was proposed recently, in which a micropapillary pattern (MPP) was described. Objectives This study aimed to evaluate the clinicopathological characteristics of LAC with MPP (LAC-MPP) and to investigate the correlation between LAC-MPP and epidermal growth factor receptor (EGFR) mutation status with the prognosis in Chinese patients. Patients and Methods From May 2007 and February 2012, Two hundred and forty-eight patients underwent resection and pathologically confirmed LAC. We classified all cases histologically according to the IASLC/ATS/ERS classification; an MPP ratio ≥ 5% was considered MPP-positive. Used Pearson's chi-square test to evaluate the relationships between EGFR mutation status and MPP status with patient clinicopathological characteristics. Results There were MPP-positive tumors (MPP ratio ≥ 5%) in 31.9% of cases (79/248); the MPP ratio correlated with TNM stage (p = 0.001) and lymph node metastasis (p = 0.03). EGFR mutation (EGFR-mut) was detected in 87 cases (34.3%); 161 cases had wild-type EGFR (EGFR-wt). EGFR mutation was present in 65% of the MPP-positive subtype. Patients with EGFR-mut tumors had significantly longer overall survival (OS) (p = 0.002). OS was also significantly longer in MPP-negative EGFR-mut or EGFR-wt patients (p < 0.001). Conclusion These findings indicate that EGFR-mut tumors are likelier to be MPP-positive subtypes and that MPP may be a novel potential pathological marker of poor prognosis in Chinese LAC patients.
    Lung Cancer 09/2014; 86(2). DOI:10.1016/j.lungcan.2014.08.018 · 3.74 Impact Factor
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    International Journal of Surgical Pathology 03/2014; 22(3). DOI:10.1177/1066896914525230 · 0.96 Impact Factor