Prevalent and up‐regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance

Nakashima, Hiroyasu; Jiang, Shi Xu; Sato, Yuichi; Hoshi, Keika; Matsumoto, Toshihide; Nagashio, Ryo; Kobayashi, Makoto; Matsuo, Yukiko; Shiomi, Kazu; Hayakawa, Kazushige; Saegusa, Makoto; Satoh, Yukitoshi

doi:10.1111/pin.12257

Cited by 16 publications

(17 citation statements)

References 32 publications

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“… 48 , 49 In recent studies, vimentin has been found to have higher expression in MPPAC, and it is correlated with higher risks of vascular invasion and lymph node metastasis. 50 , 51 In a sample of 101 MPPACs and 119 conventional ADCs of stages I–III, vimentin expression was detected by semiquantitative immunohistochemistry. Of the 101 MPPACs, vimentin expression scores of MPP and background non-MPP were 4.0±2.1 and 2.3±1.9, respectively, with a P -value of <0.0001.…”

Section: Molecular Featuresmentioning

confidence: 99%

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Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

Cao

Zhu

Jiang

et al. 2015

OTT

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Lung adenocarcinoma with a micropapillary pattern (MPPAC) has recently drawn increased attention among researchers. Micropapillary-predominant adenocarcinoma (MPA), which is defined by micropapillary pattern (MPP), is the primary histological pattern observed semiquantitatively in 5% increments on resection specimens, and MPA was formally determined to be a new histological subtype according to the new multidisciplinary classification in 2011. According to published studies, MPPAC is most common in males and nonsmokers and is associated with lymphatic invasion, pleural invasion, and lymph node metastases. MPPAC often presents as part-solid and lobulated nodules in computed tomography scans. MPP tends to have a higher maximum standardized uptake value as determined by fluorodeoxyglucose positron emission tomography combined with computed tomography, indicating a high risk of recurrence. Molecular markers, including vimentin, napsin A, phosphorylated c-Met, cytoplasmic maspin, Notch-1, MUC1, and tumoral CD10, may have higher expression in MPPAC than other subtypes; conversely, markers such as MUC4 and surfactant apoprotein A have lower expression in MPPAC. MPPAC with EGFR mutations can benefit from treatment with EGFR tyrosine kinase inhibitors. Furthermore, a complete lobectomy may be more suitable than limited resection for MPPAC because of the low sensitivity of intraoperative frozen sections and the high risk of lymph node metastasis. MPA benefits more from adjuvant chemotherapy than do other histological subtypes, whereas MPA does not benefit from adjuvant radiotherapy. Of note, MPP is associated with poor prognosis in early-stage lung adenocarcinoma, but the prognostic value of MPP is controversial in advanced-stage lung adenocarcinoma.

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Section: Molecular Featuresmentioning

confidence: 99%

“…High vimentin expression in MPP was an independent adverse prognostic factor for both overall survival (OS) and disease-free survival (DFS) (hazards ratio [HR] =1.71, 95% confidence interval [CI] =1.00–2.99, P =0.047). 51 …”

Section: Molecular Featuresmentioning

confidence: 99%

Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

Cao

Zhu

Jiang

et al. 2015

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“…In this study, the micropapillary adenocarcinoma histological subtype showed a significantly increased rate of high‐IMMT expression compared to that with other histological subtypes. Adenocarcinoma with a micropapillary pattern is characterized by more frequent and prominent vascular invasion, a higher incidence and more advanced lymph node involvement, and a poorer prognosis compared to those with conventional papillary adenocarcinoma without the micropapillary pattern . Little is known about the factors and mechanisms underlying the more aggressive nature of this tumor subtype.…”

Section: Discussionmentioning

confidence: 99%

“…Adenocarcinoma with a micropapillary pattern is characterized by more frequent and prominent vascular invasion, a higher incidence and more advanced lymph node involvement, and a poorer prognosis compared to those with conventional papillary adenocarcinoma without the micropapillary pattern. [17][18][19] Little is known about the factors and mechanisms underlying the more aggressive nature of this tumor subtype. However, IMMT might be involved in the aggressive nature of this tumor type.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of IMMT expression in surgically‐resected lung adenocarcinoma

et al. 2019

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Background Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. Methods IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan‐Meier survival analysis and Cox‐proportional hazards models were used to estimate the effect of IMMT expression on survival. Results High‐IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06–3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. Conclusion Here, we first demonstrated that high‐IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.

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“…Furthermore, most MPPAC patients are males and nonsmokers [9,12,[16][17][18][19]. Comparing with other ACs, the molecular markers of MPPAC, including vimentin, napsin A, phosphorylated c-Met, cytoplasmic maspin, Notch-1, MUC1, and tumoral CD10, are highly expressed; conversely, markers such as MUC4 and surfactant apoprotein A have low expression in MPPAC [20][21][22][23][24][25][26][27]. MPPAC has a higher frequency of epidermal growth factor receptor (EGFR) mutations and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations as compared to other histological subtypes [3,22,[28][29][30][31], while the kirsten rat sarcoma 2 viral oncogene homolog (KRAS) Results mutations or anaplastic lymphoma kinase (ALK) rearrangement are similar in all subtypes [22,[32][33][34].…”

Section: Introductionmentioning

confidence: 99%

TERT Mutation was Associated with the Risk of Recurrence in Lung Adenocarcinoma with A Micropapillary Pattern

Wang

Li²,

Hao

et al. 2020

Preprint

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Abstract Background: Lung adenocarcinoma with a micropapillary pattern (MPPAC) is the histological subtype of lung cancer. It has attracted increasing attention, especially regarding its association with poor prognosis, including the predisposition towards recurrence and metastasis. Although MPPAC has been described in early-stage cases, only a few studies have reported the correlation between disease-specific prognosis and gene mutation of MPPAC. This study aimed to clarify the common genetic mutations and the prognostic characteristics in MPPAC patients.Methods: A total of 17 patients whose surgical pathology was defined as MPPAC were followed up, the molecular characteristics were elucidated by next-generation sequencing, and the prognostic characteristics were analyzed. Results: Epidermal growth factor receptor (EGFR) mutations were identified in 11/17 (65%) of patients. TP53 alterations were identified in 10/17 (59%). Other common mutations include ATM (18%), KRAS (18%), SDHA (18%), and TERT (18%). MPPAC patients harboring EGFR and TERT mutations were at a high risk of tumor recurrence, while TP53 might be associated with a low risk of recurrence. Conclusions: TERT mutation was more frequently harbored in MPPAC patients than in the other histological type of lung cancer, and such patients were at a high risk of recurrence. So TERT mutation might be associated with adverse prognosis in MPPAC patients.

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Prevalent and up‐regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance

Cited by 16 publications

References 32 publications

Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

Prognostic significance of IMMT expression in surgically‐resected lung adenocarcinoma

TERT Mutation was Associated with the Risk of Recurrence in Lung Adenocarcinoma with A Micropapillary Pattern

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