T1 and T2 Mapping for Characterization of Mediastinal Masses: A Feasibility study.

Purpose: To evaluate the feasibility and usefulness of T1 and T2 mapping in characterization of mediastinal masses. Methods: From August 2019 through December 2021, 47 patients underwent 3.0-T chest MRI with T1 and post-contrast T1 mapping using modified look-locker inversion recovery sequences and T2 mapping using a T2-prepared single-shot shot steady-state free precession technique. Mean native T1, native T2, and post-contrast T1 values were measured by drawing the region of interest in the mediastinal masses, and enhancement index (EI) was calculated using these values. Results: All mapping images were acquired successfully, without significant artifact. There were 25 thymic epithelial tumors (TETs), 3 schwannomas, 6 lymphomas, and 9 thymic cysts, and 4 other cystic tumors. TET, schwannoma, and lymphoma were grouped together as "solid tumor," to be compared with thymic cysts and other tumors ("cystic tumors"). The mean post-contrast T1 mapping (P < .001), native T2 mapping (P < .001), and EI (P < .001) values showed significant difference between these two groups. Among TETs, high risk TETs (thymoma types B2, B3, and thymic carcinoma) showed significantly higher native T2 mapping values (P = .002) than low risk TETs (thymoma types A, B1, and AB). For all measured variables, interrater reliability was good to excellent (intraclass coefficient [ICC]: .869∼.990) and intrarater reliability was excellent (ICC: .911∼.995). Conclusion: The use of T1 and T2 mapping in MRI of mediastinal masses is feasible and may provide additional information in the evaluation of mediastinal masses.

Risk Factors for Occult Lymph Node Metastasis in Peripheral Non-Small Cell Lung Cancer with Invasive Component Size 3 cm or Less.

BACKGROUND: In the seventh edition TNM staging system for lung cancer, a high maximum standardized uptake value (SUVmax) on positron emission tomography was regarded as a risk factor for occult lymph node metastasis in clinical T1N0 non-small cell lung cancer (NSCLC). However, in the eighth edition TNM classification, tumors are classified according to the size of the invasive component only, and those with invasive component size ≤3 cm are diagnosed as stage T1. The aim of this study was to reassess the risk factors for occult lymph node metastasis under the eighth edition TNM classification for lung cancer. METHODS: From 2010 to 2017, 553 patients with clinical N0 peripheral NSCLC with invasive component size ≤3 cm underwent anatomical lobectomy with systematic lymph node dissection. We analyzed these cases retrospectively to identify risk factors for postoperative nodal upstaging. RESULTS: Among 553 study patients, 54 (9.8%) had nodal upstaging after surgery. In multivariate analysis adopting the eighth edition TNM classification for lung cancer, serum carcinoembryonic antigen (CEA) level (hazard ratio [HR] = 1.113, p = 0.002), invasive component size (HR = 2.398, p = 0.004), visceral pleural invasion (HR = 2.901, p = 0.005), and lymphatic invasion (HR = 9.336, p < 0.001) were significant risk factors for nodal upstaging, but SUVmax was not. CONCLUSION: SUVmax is not a predictor of nodal upstaging in clinical N0 peripheral NSCLC with invasive component size ≤3 cm under the eighth edition TNM classification for lung cancer. Significant risk factors of occult lymph node metastasis are serum CEA level, tumor invasive component size, visceral pleural invasion, and lymphatic invasion.

The Effect of Resection Margin Distance and Invasive Component Size on Recurrence After Sublobar Resection in Patients With Small (≤2 Cm) Lung Adenocarcinoma.

BACKGROUND: When performing sublobar resection for lung cancer, the margin distance should exceed the tumor size. However, instead of total tumor size, the 8th edition TNM staging system has adopted the size of invasive component for the T stage. The aim of this study was to determine whether the prognosis was satisfactory when the resection margin distance was greater than the invasive component size instead of the total tumor size. METHODS: From 2008 to 2017, 193 consecutive patients were diagnosed with lung adenocarcinoma (invasive component size ≤2 cm) and underwent sublobar resection. We analyzed risk factors for recurrence using clinicopathological factors including margin/invasive component ratio (resection margin distance/invasive component size). RESULTS: Mean tumor size was 1.4 (±0.5) cm and the mean invasive component size was 0.8 cm (±0.5). In the multivariate analysis, neither resection margin distance (cm) nor margin/tumor ratio (resection margin distance/tumor size) was significant risk factors for recurrence. On the other hand, the margin/invasive component ratio (hazard ratio =0.035, p = 0.043) and the SUVmax (hazard ratio =1.993, p = 0.033) were significant risk factors for recurrence. CONCLUSIONS: When sublobar resection is performed for small (invasive component size ≤2 cm) adenocarcinomas of the lung, the resection margin distance should be larger than the invasive component size. Sublobar resection is not an appropriate treatment for lung adenocarcinoma with high SUVmax.

Prognostic Factors of Pathological N1 Non-small Cell Lung Cancer After Curative Resection Without Adjuvant Chemotherapy.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with pathological N1 non-small cell lung cancer who did not receive adjuvant chemotherapy. We attempted to identify those patients for whom adjuvant chemotherapy would be indispensable. METHODS: Among 132 patients who were diagnosed with pathological N1 lung cancer at a single institution from January 2010 to December 2016 were 32 patients who did not receive adjuvant treatment after curative surgical resection. The surgical and oncological outcomes of these patients were analyzed. Candidate factors for predicting recurrence were analyzed to identify patients at high risk of recurrence. RESULTS: The median follow-up time for all 32 patients was 1044 days. The 5-year recurrence-free survival (RFS) and disease-specific survival rates of the patients without adjuvant therapy were 50.3% and 77.6%, respectively. By multivariate analysis, tumors with a lepidic growth pattern [hazard ratio (HR) 0.119, p = 0.024] and extralobar lymph node metastasis (HR 6.848, p = 0.015) were significant factors predicting recurrence. The difference between the 5-year RFS rates of patients with tumors with or without a lepidic growth pattern was statistically significant (63.5% vs 40.0%, respectively; p = 0.050). The 5-year RFS rates of patients with intralobar lymph node metastasis versus those with extralobar lymph node metastasis were 63.3% and 18.8%, respectively (p = 0.002). CONCLUSIONS: Patients with tumors without a lepidic growth pattern or with extralobar lymph node metastasis who do not receive adjuvant chemotherapy have a high recurrence rate after surgery. Therefore, these patients should be encouraged to undergo adjuvant chemotherapy if their overall condition is not a contraindication for chemotherapy.

A case of early diagnosis of pulmonary capillary hemangiomatosis in a worker with exposure to silica.

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a progressive and refractory vascular disease in the lung. Pulmonary hypertension is frequently combined with PCH when capillary proliferation invades to nearby pulmonary vascular systems. It is difficult to differentiate PCH from other diseases such as pulmonary venoocclusive disease and pulmonary arterial hypertension that cause pulmonary hypertension as they frequently overlap. CASE PRESENTATION: A 29-year-old female who had worked at a bathtub factory presented with progressive exertional dyspnea for the past 2 years. Computed tomography revealed centrilobular, diffusely spreading ground-glass opacities sparing subpleural parenchyma with some cystic lesions and air-trapping in both lungs, suggesting a peculiar pattern of interstitial lung disease with airway involvement. There was not any evidence of right heart failure or pulmonary hypertension on echocardiogram, as well as radiography. Microscopic examination of the lung by thoracoscopic resection showed atypical proliferation of capillary channels within alveolar walls and interlobar septa, without invasion of large vessels. CONCLUSION: We experienced a pathologically diagnosed PCH in a young female complaining progressive dyspnea with prior exposure to occupational silica or organic solvent without elevated right ventricular systolic pressure (RVSP) who showed atypical pattern of radiologic findings.

Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung.

Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and ß-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent ß-catenin mutations (overall 3 of 68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Because the AKT1 mutations were not found to co-occur with ß-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be the single-most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas, including a high rate of AKT1 mutation in PSHs. These genomic features of PSH identified in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors.

Lymphovascular Invasion Increases the Risk of Nodal and Distant Recurrence in Node-Negative Stage I-IIA Non-Small-Cell Lung Cancer.

OBJECTIVES: Despite complete surgical resection, 30-40% of patients with stage I-IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1-2N0 NSCLC. METHODS: We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1-2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. RESULTS: LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). CONCLUSIONS: LVI is a negative prognostic factor in patients with stage I-IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence.

Margin Width of Resected Lepidic Lung Cancer Does Not Affect Recurrence After Sublobar Resection.

BACKGROUND: A sufficient resection margin is required for the sublobar resection of lung cancers. However, the width of the resection margin may not be important in lepidic adenocarcinoma, because such tumors are non- or minimally invasive. The purpose of this study was to determine the effect of resection margin width on the outcome of patients with lepidic-dominant adenocarcinoma after sublobar resection. METHODS: This study included 133 patients with small (≤2 cm), clinical N0M0 lung cancer who underwent sublobar resection with curative intent. The patients were divided into 4 groups: Group A, lepidic tumor with margin/tumor ratio <1; Group B, lepidic tumor with margin/tumor ratio ≥1; Group C, non-lepidic tumor with margin/tumor ratio <1; Group D, non-lepidic tumor with margin/tumor ratio ≥1. The clinicopathological features and survival outcomes between Group A and B patients, and between Group C and D patients were compared. RESULTS: The 5-year recurrence-free survival (RFS) rates of Group A and B patients were both 100%. The 5-year RFS rates of Group C and D patients were 49.9 and 97.1%, respectively (p = 0.009). By multivariate analysis, the margin/tumor ratio was a significant independent factor for recurrence in patients with non-lepidic tumors (hazard ratio = 0.157, 95% confidence interval 0.027-0.898; p = 0.037). CONCLUSIONS: Tumor recurrence after sublobar resection is not associated with short resection margins in patients with lepidic tumors. However, a short resection margin is a significant risk factor for recurrence in patients with non-lepidic tumors.

Consolidation/Tumor Ratio on Chest Computed Tomography as Predictor of Postoperative Nodal Upstaging in Clinical T1N0 Lung Cancer.

BACKGROUND: In clinical T1N0 peripheral lung cancers, lymph node upstaging is occasionally encountered postoperatively. However, nodal upstaging is rare in lung cancers presenting as ground-glass opacities. The aim of this study was to determine if lymph node upstaging could be reliably extrapolated from parameters such the consolidation/tumor ratio of chest computed tomography. METHODS: We conducted a retrospective study of 486 patients treated for peripheral clinical T1N0 non-small cell lung cancer, each undergoing lobectomy with mediastinal lymph node dissection. We compared preoperative variables in the pathologic N0 and nodal upstaging groups, analyzing such variables to determine factors predictive of lymph node upstaging. RESULTS: Of the 486 patients studied, lymph node upstaging occurred in 42 (8.6%). In the upstaging group, the mean nodule diameter exceeded that of the pathologic N0 group (2.3 vs 1.9 cm, respectively; p < 0.001), and the mean consolidation/tumor ratio was larger in the upstaging group than the pN0 group (0.95 vs 0.68, respectively; p < 0.001). Nodule diameter and consolidation/tumor ratio emerged as significant predictive factors for lymph node upstaging after surgery in a multivariate analysis (hazard ratio [HR] 2.259, p = 0.039; HR 173.645, p = 0.001, respectively). CONCLUSIONS: Consolidation/tumor ratio and nodule diameter are significant predictive factors of postoperative lymph node upstaging. The higher the consolidation/tumor ratio and smaller the nodule diameter, the less likely the occurrence of postoperative lymph upstaging would be in clinical T1N0 peripheral non-small cell lung cancer.

Clinical Significance of C-MET Overexpression and Epidermal Growth Factor Receptor Mutation in Platinum-Based Adjuvant Chemotherapy Outcome in Surgically Resected Lung Adenocarcinoma.

PURPOSE: We retrospectively assessed the role of C-MET expression and epidermal growth factor receptor (EGFR) mutation on survival following platinum-based adjuvant chemotherapy. The impact of C-MET on survival was also investigated in relation to EGFR mutation status. METHODS: We enrolled 311 patients with resected lung adenocarcinoma (high-risk stage 1B-3A), and performed immunohistochemistry (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue microarrays. RESULTS: Adjuvant chemotherapy was administered to 151 patients, 96 of whom relapsed and 85 died by the end of the study. On IHC, C-MET and EGFRmut were positive in 141 (45.3 %) and 88 (28.3 %) cases, respectively. On univariate analysis, adjuvant chemotherapy prolonged relapse-free survival (RFS) and overall survival (OS) in C-MET(+) patients (RFS p = 0.035; OS p = 0.013) but not in C-MET(-) patients. On multivariate analysis, adjuvant chemotherapy was a positive independent prognostic factor in C-MET(+) (RFS p = 0.013; OS p = 0.006) but not in C-MET(-) patients. In addition, univariate analysis showed no effect of EGFRmut status on RFS and OS after chemotherapy, whereas multivariate analysis revealed that adjuvant chemotherapy increased RFS in both EGFRmut(+) and EGFRmut(-) patients [EGFRmut(+) p = 0.033; EGFRmut(-) p = 0.030]. C-MET was a negative prognostic factor for RFS (p = 0.045) and OS (p = 0.007) in the EGFRmut(-) group but not in the EGFRmut(+) group, on multivariate analysis. CONCLUSIONS: Our data indicate that patients with C-MET overexpression should be considered for adjuvant chemotherapy, and that C-MET negatively correlates with survival in patients with wild-type, but not mutant, EGFR.

Prognosis After Sublobar Resection of Small-sized Non-small Cell Lung Cancer with Visceral Pleural or Lymphovascular Invasion.

BACKGROUND: Although standard surgical treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy, sublobar resection may be elected for small-sized (≤2 cm) peripheral tumors. Our aim was examine the need for completion lobectomy in the event of confirmed pleural or lymphovascular invasion after sublobar resection of NSCLC. METHODS: A total of 271 consecutive patients undergoing curative resection of stage I NSCLC ≤2 cm were reviewed retrospectively, analyzing clinicopathologic findings and survival times of those with invasion-positive (visceral pleural or lymphovascular invasion) or invasion-negative (neither visceral pleural nor lymphovascular invasion) tumors by surgical approach (sublobar resection vs lobectomy). RESULTS: Aside from age and pulmonary function, clinicopathologic characteristics of the patient subsets did not differ significantly, nor did 5-year recurrence-free survival rates of surgical subsets (sublobar resection vs lobectomy) in respective tumor groups (invasion-positive 78.9 vs 79.8%, p = 0.928; invasion-negative 80.2 vs 85.4%, p = 0.505). In multivariate analysis, dissected lymph node count was the sole parameter significantly impacting recurrence of stage I invasion-positive NSCLC (hazard ratio = 0.914, 95% confidence interval 0.845-0.988; p = 0.023). Sublobar resection was not a risk factor for recurrence. CONCLUSIONS: Survival rates for patients with small-sized (≤2 cm) NSCLC and visceral pleural or lymphovascular invasion did not differ significantly, whether sublobar resection or lobectomy was done. Hence, completion lobectomy is unnecessary in this setting.

Sublobar Resection Margin Width Does Not Affect Recurrence of Clinical N0 Non-small Cell Lung Cancer Presenting as GGO-Predominant Nodule of 3 cm or Less.

BACKGROUND: Sublobar resection of lung cancer may benefit patients with lung cancer presenting as ground-glass opacity (GGO) nodules. The purpose of this study was to evaluate the effect of margin width on recurrence after sublobar resection in patients with clinical N0 non-small cell lung cancer presenting as GGO-predominant nodule. METHODS: We conducted a retrospective chart review of 91 patients treated for clinical N0 non-small cell lung cancer ≤3 cm by sublobar resection with clear resection margins. We assigned them to two groups: GGO-predominant tumor and solid-predominant tumor. Each group was subdivided into two groups according to the margin width: resection margin ≤5 mm and resection margin >5 mm. We analyzed the clinicopathological findings and survival among these four groups. RESULTS: There was no recurrence in GGO-predominant tumors after sublobar resection. Margin width did not influence the recurrence in GGO-predominant tumors. In the cases of solid-predominant tumor, 5-year recurrence-free survival after sublobar resection according to margin width ≤5 and >5 mm was 24.2 and 79.6 %, respectively (p < 0.001). Therefore, narrow margin width (resection margin ≤5 mm) was a significant risk factor for recurrence of solid-predominant tumors (hazard ratio 3.868, 95 % confidence interval 1.177-12.714, p = 0.026). CONCLUSIONS: The width between the tumor and resection margin does not affect the recurrence after R0 sublobar resection in patients with clinical N0 GGO-predominant lung cancer ≤3 cm. By contrast, margin width is a significant risk factor for recurrence after sublobar resection in patients with clinical N0 solid-predominant lung cancer.

Lymphatic invasion is a more significant prognostic factor than visceral pleural invasion in non-small cell lung cancer with tumours of 3 cm or less.

BACKGROUND AND OBJECTIVE: Visceral pleural invasion is an upstaging factor that increases cancer staging from stage IA to IB for tumours of 3 cm or less. However, lymphatic invasion has not been associated with the tumour-node-metastasis (TNM) staging system. The purpose of this study was to compare visceral pleural invasion and lymphatic invasion as prognostic factors. METHODS: We retrospectively reviewed 353 consecutive patients who underwent curative resection for stage I non-small cell lung cancer (NSCLC) tumours of 3 cm or less. Patients were divided into three groups and compared. Group A contained no invasions; group B contained visceral pleural invasion only and group C had lymphatic invasion only. RESULTS: Group A patients had stage IA, but group B patients had stage IB tumours. However, group C patients had stage IA tumours. The 5-year recurrence-free survival for the three groups was 86.2%, 71.5% and 48.0%, respectively. There was a significant difference in survival between groups A and C (P = 0.001).Survival was not different between groups A and B (P = 0.547). In a multivariate analysis conducted to determine risk factors for recurrence, lymphatic invasion was a significant independent risk factor for recurrence (hazard ratio = 2.570, P = 0.006). Pleural invasion was not a significant risk factor for recurrence. CONCLUSION: Lymphatic invasion is a more significant prognostic factor than visceral pleural invasion in NSCLC of 3 cm or less.

Leukemic infiltration presenting as myocardial hypertrophy after complete remission of acute myeloid leukemia.

Here, we report a rare case of isolated leukemic infiltrate of the myocardium (extramedullary involvement) presenting as restrictive cardiomyopathy in a patient in complete remission of acute myeloid leukemia. It was evaluated with multimodality imaging studies (echocardiography and cardiac MRI) and further confirmed by pathology. The present case highlights the importance of maintaining a high degree of clinical suspicion when evaluating patients with progressive ventricular hypertrophy of unknown cause, including recognition of the potential involvement by recurrent hematologic malignancy.

Pseudozyma aphidis fungaemia with invasive fungal pneumonia in a patient with acute myeloid leukaemia: case report and literature review.

Pseudozyma species rarely cause invasive diseases in humans, which are usually isolated from plants. There have been anecdotal reports regarding Pseudozyma species infections in patients with underlying diseases or in neonates. However, clinical data and the pathogenicity in humans are still insufficient. We experienced a case of Pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51-year-old male with acute myeloid leukaemia (AML). P. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rDNA gene sequencing analysis. The patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the AML and infectious complications. Here, we report a case of P. aphidis infection that developed during neutropenia in an AML patient and review the global literature.

The importance of the lepidic component as a prognostic factor in stage I pulmonary adenocarcinoma.

BACKGROUND: Stage I pulmonary adenocarcinoma (PA) can offer an unfavorable prognosis. The aim of this study was to classify the prognosis of stage I PA on the basis of the lepidic component and to confirm whether the lepidic component can be used as a criterion for predicting the prognosis of stage I PA. METHODS: We conducted a retrospective study of patients who underwent curative surgery for stage I and IIA PA. Stage I disease was divided into three groups on the basis of the lepidic component: group 1, ≤10%; group 2, >10 to 50%; and group 3, >50%. We compared recurrence-free survival (RFS) rates among groups 1, 2, and 3, and stage IIA disease. We also evaluated risk factors for disease recurrence with multivariate analysis. RESULTS: A total of 224 patients were included in our study; most patients (n=201) had stage I disease. Three-year RFS rates in group 1 (n=73), group 2 (n=75), and group 3 (n=53) were 74.1, 90.4, and 90.0%, respectively. There was a significant difference in RFS between group 1 and group 2 (p=0.009). The 3-year RFS rate in stage IIA disease was 61.4%. There were no significant differences in RFS between group 1 and stage IIA disease (p=0.163). In multivariate analysis, group 1 had the highest risk of recurrence (HR 5.806, p=0.006) in stage I PA. CONCLUSIONS: Stage I PA with a lepidic component≤10% was associated with an unfavorable prognosis that was similar to the prognosis of stage IIA disease. The prognosis for stage I PA should not be based on general criteria, but instead, the lepidic component should be evaluated and considered when determining disease prognosis.

Bis Expression in Patients with Surgically Resected Lung Cancer and its Clinical Significance.

BACKGROUND: Bis, also known as BAG3, has been identified as a Bcl-2-interacting protein that enhances cellular anti-apoptotic activity. It is involved in cellular differentiation, angiogenesis, migration, and invasion in various tumors. The purpose of this study was to investigate the Bis expression pattern, and the clinical significance thereof, in patients with resected lung cancer. METHODS: We studied 121 lung cancer patients who underwent curative surgical resection. Patient clinicopathological characteristics were reviewed retrospectively from medical records, including tumor recurrence and survival. The expression of Bis protein in lung cancer tissues was evaluated by immunohistochemical staining and was assessed using a four-tiered intensity score system (negative, weak, moderate, strong). Enhanced Bis expression at the periphery of a tumor facing the adjacent nontumor region was referred as "marginal activity." RESULTS: Although Bis expression was higher in squamous cell carcinoma than in adenocarcinoma, marginal activity was higher in adenocarcinoma than in squamous cell carcinoma. All of the small cell carcinomas and lung cancer with neuroendocrine differentiation examined were negative for Bis expression. Compared with stage I lung cancer, patients with stage II and IIIA lung cancer exhibited higher Bis protein levels in lung tissues. Recurrence and survival rates did not differ significantly according to Bis expression intensity score or marginal activity. CONCLUSIONS: Our study demonstrated that Bis expression differed according to the histological type and pathological stage of the lung cancer. Further studies are needed to assess its use as a biomarker and its role in the molecular pathogenesis of lung cancer.

Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage.

BACKGROUND: Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized. METHODS: We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner. RESULTS: Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10-15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than <10% ALK FISH split group. CONCLUSIONS: Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease.

Correlation of histological components with tumor invasion in pulmonary adenocarcinoma.

BACKGROUND: Pulmonary adenocarcinoma (PA) is the most common histologic type of primary lung cancer. Generally, adenocarcinoma was composed by five major components. The present study aimed to evaluate changes in the composition of adenocarcinoma components as the tumor grows; in addition, to analyze the correlation between the occupancy rates of histologic components of the tumor in regard to prognosis. METHODS: Pathologic data were retrospectively evaluated for 206 patients who underwent curative resection of PA. We investigated how histologic component occupancy rates changed as tumor size and N stage increased. To evaluate local invasiveness, the major components of the present group and absent group of pleural invasion, lymphatic invasion, and vascular invasion were compared. RESULTS: The mean percentages of acinar and solid components significantly increased with an increase in size (P = 0.006, P < 0.001) ; however, the percentage of lepidic components decreased (P < 0.001). In cases with a solid component and a micropapillary component, a gradual increase was found with an increase N stage (P = 0.001, P < 0.001); however the percentage of lepidic components decreased (P < 0.001). Average differences of histologic components dependent upon whether pleural, lympathic and vascular invasion were present, the difference of micropapillary and lepidic components were statistically significant. With logistic regression analysis, as the occupancy rate of the lepidic component increased, the probability of pleural invasion, lymphatic invasion, and vascular invasion decreased; in cases with a micropapillary component, as the occupancy rate of increased, the probability of lymphatic invasion and vascular invasion increased. In multivariate analysis using the Cox propotional hazards model, the occupancy rates of acinar(p = 0.043; odds ratio = 1.023), micropapillary(p = 0.002; odds ratio = 1.051) and lepidic (p = 0.005; odds ratio = 0.966) components were significantly associated with recurrence. CONCLUSIONS: The lower the occupancy rate of a lepidic component and the higher the occupancy rates of acinar, solid, and micropapillary components, the likelihood of tumor progression increased. In addition, as the occupancy rate of a lepidic component decreased and a micropapillary component increased, local invasiveness and recurrence rate increased; thus, increasing the probability of a poor prognosis.