Micropapillary lung adenocarcinoma: a distinctive histologic subtype with prognostic significance. Case series.
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: Selective activation of Rho GTPase cascade requires the release of Rho from RhoGDI (GDP-dissociation inhibitors) complexes. Our previous studies identified RhoGDIα SUMOylation at Lys-138 and its function in the regulation of cancer cell invasion. In the current study, we demonstrate that RhoGDIα SUMOylation has a crucial role in the suppression of cancer cell anchorage-independent growth as well as the molecular mechanisms underlying this suppression. We found that ectopic expression of RhoGDIα resulted in marked inhibition of an anchorage-independent growth with induction of G0/G1 cell cycle arrest, while point mutation of RhoGDIα SUMOylation at residue Lys-138 (K138R) abrogated this growth suppression and G0/G1 cell cycle arrest in cancer cells. Further studies showed that SUMOylation at Lys-138 was critical for RhoGDIα down-regulation of cyclin D1 protein expression and that MEK1/2-Erk was a specific downstream target of SUMOylated RhoGDIα for its inhibition of C-Jun/AP-1 cascade, cyclin d1 transcription, and cell cycle progression. These results strongly demonstrate that SUMOylated RhoGDIα suppressed C-Jun/AP-1-dependent transactivation specifically via targeting MEK1/2-Erk, subsequently leading to the down-regulation of cyclin D1 expression and anti-cancer activity. Our results provide new mechanistic insights into the understanding of essential role of SUMOylation at Lys-138 in RhoGDIα's biological function.Molecular oncology 12/2013; · 6.70 Impact Factor
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ABSTRACT: Background: Papillary thyroid carcinoma (PTC) is increasing in incidence while mortality is unchanged. Identifying patients with higher risk of recurrence and death is essential. Case series identify the hobnail variant of PTC (HVPTC), which is characterized by micropapillary architecture, apocrine features and loss of cellular polarity. Herein, we describe the clinical course, pathological features, and mutational profile of patients at our institution with HVPTC. Methods: A query into the surgical pathological database (2009-2012) was performed and clinicopathological data were collected on all patients carrying the diagnosis of HVPTC. BRAFV600E testing was performed on paraffin-embedded blocks using SNaPshot mutational analysis. Results: Twelve patients with the HVPTC were identified with an average age of 54.1 ± 18.8 years. Seven patients (63.6%) were AJCC Stage III or IV at presentation. Tumors were large (3.7 ± 2.0 cm), some were multifocal (33.3%), and frequently with extra-thyroidal extension (58.3%), lymphovascular invasion (41.7%), and lymph node metastasis (75%). Fourty-percent of the patients had concomitant tall cell features (TCF) and two had small foci of undifferentiated (anaplastic) thyroid carcinoma (ATC). Eight out of ten (80%) tumors undergoing mutational analysis had the BRAFV600E mutation, and the remainder two cases (20%) harbored a RET/PTC1 gene rearrangement. No other known thyroid cancer mutations were identified on SNaPshot analysis. At median follow-up of 26 months, four patients had recurrent or persistent disease, one of whom died from the disease one year after surgery.Thyroid: official journal of the American Thyroid Association 01/2014; · 2.60 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; · 3.74 Impact Factor