Variants Of Invasive Adenocarcinoma Research Articles

A retrospective study of the relationship between the pathologic subtype and lymph node metastasis of lung adenocarcinomas of ≤3 cm diameter.

To analyze the relationship between pathologic subtype and lymph node metastasis for lung adenocarcinomas of ≤3 cm diameter.We retrospectively studied 384 patients with operable lung adenocarcinomas of ≤3 cm diameter that had been radically resected by lobectomy or anatomic segmentectomy with systematic nodal dissection, at the Fujian Medical University Union Hospital between March 2014 and March 2016.Lymph node metastasis pN1 + pN2 (pN+) was found in 2 of 104 (1.9%) patients with tumor diameter ≤1.0 cm, 12 of 159 (7.5%) patients with tumor diameter >1.0 cm but ≤2.0 cm, and 35 of 121 (28.9%) patients with tumor size >2.0 cm but ≤3.0 cm (P < .01). Lymph node metastasis pN+ was found in 19 of 53 (35.8%) patients with visceral invasion pleural (VIP) and 30 of 331 (9.0%) patients without VIP (P < .05). It was also found in 16 of 51 (31.3%) patients with high serum CEA concentrations and 28 of 297 (9.4%) patients with normal concentrations (P < .05). In a multivariate analysis, tumor diameter, VIP, high serum CEA concentration, and pathologic subtype were significant risk factors. The prevalences of lymph node metastasis pN+ were: 0.0% (0/2), 0.0% (0/89), 3.2% (1/31), 16.2% (34/209), 7.7% (1/13), 46.7% (7/15), 100% (4/4), and 11.8% (2/17) for adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); predominantly lepidic (LEP), acinar (ACI), papillary, solid (SOL), and micropapillary (MIP) tumors; and variants of invasive adenocarcinoma, respectively (P < .05). For predominant SOL and MIP tumors, the prevalences of lymph node involvement were significantly higher than for the other subtypes.We have shown that lymph node metastasis in patients with tumor diameter ≤3 cm differs according to lung adenocarcinoma subtype. AIS and MIA were not associated with lymph node metastasis; therefore, systematic nodal dissection may be unnecessary. The prevalence of lymph node metastasis rate was low for LEP, suggesting that systemic lymph node sampling is sufficient. In contrast, for other pathologic subtypes, including SOL and MIP, systematic lymph node dissection should be performed.

Prognostic significance of anaplastic lymphoma kinase rearrangement in patients with completely resected lung adenocarcinoma.

Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I-IIIA lung adenocarcinoma. Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I-IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status. Among 2,103 stage I-IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33-1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22-1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01-9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07-3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43-17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043). ALK rearrangement was not an independent prognostic factor in stage I-IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.

Frequencies of actionable mutations and survival in variants of invasive adenocarcinoma of lung

Background: The objective of the present study was to explore the common actionable mutations and survival in variants of invasive adenocarcinoma (VIA) of lung.

Frequencies of actionable mutations and survival in variants of invasive adenocarcinoma of lung

Background: The objective of the present study was to explore the common actionable mutations and survival in variants of invasive adenocarcinoma (VIA) of lung. Methods: A total of 1,120 lung adenocarcinoma patients with pathologically confirmed VIA and completely resected stage I–IIIA were enrolled from 2010 to 2013. For comparison, we evaluated the gene status and survival of 380 non-VIA lung adenocarcinoma patients. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 and fusions of ALK, ROS1 and RET. Survival curves were plotted with Kaplan-Meier method. Results: Thirty-one patients were selected, including invasive mucinous adenocarcinoma (n=15), enteric adenocarcinoma (n=9), colloid adenocarcinoma (n=4) and fetal adenocarcinoma (n=3). The overall frequency of gene abnormality was 48.4% (15/31) in VIA. The gene abnormalities were as follows: KRAS mutation (n=5), ALK rearrangement (n=4), PIK3CA mutation (n=2), EGFR mutation (n=2), HER2 mutation (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were observed. The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs. 74.7%, P=0.0015). No difference in recurrence-free survival (RFS) was found between VIA and non-VIA patients (38.0 vs. 47.0 months, P=0.524). There was a trend of worse overall survival (OS) in VIA than non-VIA patients (48.0 vs. 57.0 months, P=0.052). Conclusions: As a rare type of lung adenocarcinoma, VIA has a lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma is the most frequent subtype and KRAS represents a predominant actionable mutation in VIA patients. There is a trend of worse survival in VIA than non-VIA patients.

Lymph node involvement influenced by lung adenocarcinoma subtypes in tumor size ≤3 cm disease: A study of 2268 cases

AimsWhether lung adenocarcinoma subtype has influence on lymph node involvement in small-sized lung cancer is still unclear. If it has, we want to clarify the extent of the impact. MethodsWe identified 2268 operable lung adenocarcinoma patients with tumor size ≤ 3 cm who had undergone a lobectomy and systematic nodal dissection at Shanghai Chest Hospital between July 2012 and December 2014. The histologic subtypes of all patients were classified according to the IALSC/ATS/ERS classification. The relationship between lymph node involvement and clinicopathologic characteristics was evaluated. ResultsLymph node involvement (pN1+ pN2) was found in 7 of 220 (3.2%) patients with tumor size ≤ 1.0 cm, 173 of 1196 (14.5%) patients with tumor size >1.0, ≤2.0 cm, and 265 of 852 (31.1%) patients with tumor size > 2.0, ≤3.0 cm. Among all 2268 patients, the percentages of lymph node involvement (pN1+ pN2) were: 47.6%, 47.2%, 24.0%, 18.9%, 18.1%, 0%, 0%, and 0% for solid predominant (Sol), micropapillary predominant (MIP), variants of invasive adenocarcinoma (VIA), papillary predominant (Pap), acinar predominant (Aci), lepidic predominant (Lep), minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), respectively. For Sol and MIP, the percentages of lymph node involvement were significantly higher than other subtypes, 50.0% and 66.7% in tumor size ≤ 1.0 cm, 42.0% and 38.6% in tumor size > 1.0, ≤2.0 cm, 52.2% and 55.7% in tumor size > 2.0, ≤3.0 cm. ConclusionOur study revealed that lung adenocarcinoma subtypes had important role in lymph node involvement for the patients with small-sized lung cancer.

Correlation of survival and EGFR mutation with predominant histologic subtype according to the new lung adenocarcinoma classification in stage IB patients.

BackgroundA new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been published. This study aimed to investigate the utility of the new histological classification for identifying the prognostic subtypes of adenocarcinomas in stage IB patients.Correlations between the classification and the presence of epidermal growth factor receptor (EGFR) mutation status was also studied.MethodsOne hundred and thirty-six patients with stage IB lung adenocarcinoma operated on in Zhejiang Cancer Hospital were identified between 2002 and 2011. Patients overall survival and disease-free survival were calculated using Kaplan-Meier and Cox regression analyses. EGFR mutations were detected using the amplification refractory mutation system.ResultsA total of 136 cases were included in current study, of which 38 were papillary predominant, 39 were acinar predominant, 22 were micropapillary predominant, 21 were lepidic predominant subtypes, 14 were solid predominant, and 2 were variants of invasive adenocarcinoma. Patients with micropapillary- and solid-predominant tumors had the lowest five-year disease-free survival (28.4 and 36.7%, respectively). Univariate and multivariate analysis showed that the micropapillary-predominant subtype was an independent predictor of disease-free survival (P = 0.0041 and 0.048, respectively), but not overall survival (P = 0.175 and 0.214, respectively). EGFR mutations were significantly associated with the micropapillary-predominant subtype patients (P = 0.0026). The EGFR mutation frequency is lower in the solid-predominant subtype than other subtypes (P = 0.0508).ConclusionsThe predominant subtype in the primary tumor was associated with prognosis in resected stage IB lung adenocarcinoma. The EGFR mutation frequency of micropapillary-predominant subtype is higher than other subtypes.

Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients—Based on a hospital study in China

We investigated the relationship between predominant subtype, according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, and prognosis in stage I lung adenocarcinoma in Zhejiang Cancer Hospital. Two hundred and sixty-one patients with stage I lung adenocarcinoma, operated in Zhejiang Cancer Hospital, were identified between 2000 and 2010. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. None of the cases were adenocarcinoma in situ and six were minimally invasive adenocarcinomas. Two hundred and fifty-five cases were invasive adenocarcinoma. Of those, 80, 76, 42, 34, 19, and 4 were papillary predominant, acinar predominant, micropapillary predominant, solid predominant, lepidic predominant subtypes, and variants of invasive adenocarcinoma, respectively. Patients with micropapillary and solid predominant tumors had a significantly worse disease-free survival as compared to those with other subtypes predominant tumors (p < 0.001). Multivariate analysis revealed that the new classification was an independent predictor of the disease-free and overall survival (p = 0.002 and 0.015). The predominant subtype in the primary tumor was associated with prognosis in resected stage I lung adenocarcinoma.

Prognostic significance of the IASLC/ATS/ERS classification in Chinese patients—A single institution retrospective study of 292 lung adenocarcinoma

A new classification of pulmonary adenocarcinoma has been recently proposed by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS). This study was undertaken in an attempt to explore the clinical implication of this new classification in Chinese patients. Two hundred ninety-two lung adenocarcinomas were reclassified strictly according to the IASLC/ATS/ERS classification by two pathologists, independently. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the new classification and patients' prognosis. We confirmed three groups with different outcomes. Both AIS and MIA had 100% 5-year disease-free survival rate and 100% 5-year overall survival rate. Lepidic, acinar, and papillary as well as variants of invasive adenocarcinoma had intermediate prognosis. Solid and micropapillary cases had poor prognosis (DFS: P < 0.001, OS: P = 0.002). After controlling the clinicopathological factors, the new classification was identified as an independent prognostic factor in patients' disease-free survival and overall survival. We have demonstrated a valuable prognostic role of the new classification in Chinese patients. This new classification is valuable of screening out patients with high risk of recurrence to receive postoperative adjuvant therapy.

Rare subtypes of adenocarcinoma of the lung

The 1999 WHO classification of adenocarcinoma of the lung and pleural tumors listed five rare variants of adenocarcinoma of the lung: well-differentiated fetal adenocarcinoma, colloid ‘mucinous’ adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma and clear-cell adenocarcinoma. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society developed a multidisciplinary, international classification of lung adenocarcinoma that was published in the February 2011 issue of the journal of Thoracic Oncology. This most current classification lists four rare variants of invasive adenocarcinoma of the lung: invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid adenocarcinoma (retained and expanded), fetal adenocarcinoma (retained) and enteric adenocarcinoma (new). Signet ring adenocarcinoma and clear-cell adenocarcinoma were removed from the list of variants of adenocarcinoma of the lung. Mucinous cystadenocarcinoma was merged into colloid adenocarcinoma. The new 2011 classification also takes into consideration of the amount of tissue sample available according to the two major methods how the tumor is procured: resection specimens versus small biopsy/cytology. Rare variants of invasive adenocarcinoma of the lung will only now be classified from resection specimens where adequate architecture of tumor can be identified.