Nectin‐like molecule‐5 (Necl‐5) is an immunoglobulin (Ig)‐like molecule that is up‐regulated in many types of cancer cells. It was shown experimentally that Necl‐5 enhances cell migration, ...proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl‐5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl‐5. The relationship between expression of Necl‐5 and clinicopathological features was analyzed, and the influence of Necl‐5 expression on outcomes in these patients was assessed. A strong expression of Necl‐5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl‐5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease‐free survival rate in patients with positive Necl‐5 overexpression was significantly lower than that in patients with negative Necl‐5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl‐5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease‐free survival rate of the Necl‐5‐positive group was significantly lower than that of the Necl‐5‐negative group (P = 0.0192). These results indicate that Necl‐5 plays a role in mediating tumor cell invasion and that the overexpression of Necl‐5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma.
(Cancer Sci 2010; 101: 1326–1330)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background This study compares long-term prognosis of intentional extended segmentectomy and lobectomy of clinical T1aN0M0 non-small cell lung cancer (NSCLC). Risk factors of local-regional ...recurrence are identified and segmentectomy outcomes are examined per segment. Methods 164 intentional extended segmentectomies were compared with 73 lobectomies subcategorized by consolidation to maximum tumor diameter ratio (C/T) measured by computed tomographies. Preoperative characteristics were propensity score matched to evaluate local-regional recurrence-free survival using the log-rank test. Preoperative factors and surgical procedure were analyzed with the Cox proportional hazards regression model to identify independent predictor of local-regional recurrence. Local-regional recurrence per segment were assessed by Kaplan-Meier estimates between both groups. Results No recurrences were observed for 46 C/T ≤0.5 segmentectomies. In 59 C/T >0.5 propensity score-matched pairs, 5-year local-regional recurrence-free survival rates of segmentectomies were 76.3%, versus 91.5% for lobectomies ( p = 0.082). Multivariate analysis confirmed segmentectomies to be the only independent risk factor for local-regional recurrence-free probability ( p = 0.020). Subset analysis reveals superior segmentectomies have significantly less local-regional recurrence ( p = 0.029) than other segments and comparable prognosis to lower lobectomies. Left upper lobe segmentectomies also showed comparable prognosis to lobectomies. Segmentectomies in the right upper lobe and of basal segments showed significantly higher local recurrence ( p = 0.001) than other segments. Basal segmentectomies showed significantly poor prognosis versus lower lobectomies ( p = 0.005). Conclusions For radiographically invasive right upper lobe or basal segment clinical T1a NSCLC, strict inclusion criteria is necessary for intentional segmentectomy. For superior and left upper lobe segments, however, segmentectomies may be preferred with prognosis comparable to lobectomies.
The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung ...cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio HR, 0.52; 95% confidence interval CI, 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
This manuscript reports a subgroup analysis of Japanese patients in the global phase 3 IMpower010 study evaluating adjuvant atezolizumab vs best supportive care (BSC) following platinum‐based chemotherapy in resected stage IB‐IIIA non‐small cell lung cancer. Disease‐free survival (DFS) improvement with atezolizumab versus BSC was observed in the Japanese stage II‐IIIA population with PD‐L1 expression on ≥1% of tumor cells; in the Japanese all‐randomized stage II‐IIIA and ITT (stage IB‐IIIA) populations, unstratified DFS hazard ratios favored atezolizumab vs BSC. Adjuvant atezolizumab had a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
EWSR1‐CREM gene fusions were recently discovered in several mesenchymal and epithelial tumors, including myxoid mesenchymal tumors of the central nervous system, rare cases of soft tissue clear cell ...sarcoma and angiomatoid fibrous histiocytoma, and hyalinizing clear cell carcinoma, which implicates the potential phenotypic diversities of tumors harboring an EWSR1‐CREM fusion. We herein present an exceedingly indolent pulmonary mesenchymal tumor showing distinctive clinicopathological features. This tumor histologically displayed a small nest and alveolar pattern consisting of monomorphic clear cells intermingled with dilated anastomosing vasculature. Immunophenotypically, tumor cells were positive for vimentin and focally positive for synaptophysin, but negative for many immunohistochemical panels including keratins, EMA, desmin, mesothelial markers, melanotic markers, smooth muscle actin, inhibin and S‐100 protein. Interestingly, RNA sequencing identified an in‐frame EWSR1‐CREM fusion, which was confirmed by subsequent real‐time/reverse transcription polymerase chain reaction and fluorescence in situ hybridization assay. Clinical follow‐up showed no evidence of recurrence and metastasis. Our pathological findings further expand the phenotypic spectrum of tumors associated with EWSR1‐CREM fusions, implying the emergence of a possible novel tumor entity.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The GINS complex associates with cell division cycle (Cdc) protein 45 and mini‐chromosome maintenance (Mcm) proteins 2–7 to form the Cdc45–Mcm–GINS (CMG) complex, which is essential for DNA ...duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non‐small‐cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.
Our investigation of surgically resected specimens from patients with non‐small‐cell lung cancer (NSCLC) revealed that Psf3 expression was strongly correlated with tumor progression in NSCLC. Moreover, Psf3 acted as the CMG complex, which could lead to excessive proliferation. These findings provide clues regarding the role of Psf3 in NSCLC, and could yield novel molecular‐targeted treatment strategies aimed at inhibiting the pathways that lead to the proliferation and progression of NSCLC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
DNA damage response pathways are important for maintaining genomic stability. The oncogenic phosphatase Wip1 plays a crucial role in DNA damage response by inhibiting several cell cycle proteins, ...including p53. Although Wip1 gene amplification has been reported in various primary tumors, including lung cancer, its biological significance for survival of primary lung tumor patients remains unclear. We investigated the expression of Wip1 in cancer epithelial cells immunohistochemically in 84 consecutive resected cases of lung adenocarcinoma. Increased Wip1 expression was observed in 54 (64.3%) of the 84 cases. Wip1 expression was found to be correlated significantly with two clinicopathological factors: γ‐H2AX expression, and invasion to the pulmonary vein. A univariate analysis and log–rank test indicated a significant association between Wip1 expression and lower overall survival rate (P = 0.019 and P = 0.0099, respectively). A multivariate analysis also indicated a statistically significant association between increased Wip1 expression and lower overall survival rate (hazard ratio, 4.3; P = 0.026). The Ki67 index level was higher in the Wip1‐positive group than in the negative group (P < 0.04, Mann–Whitney U‐test). Moreover, in a subgroup analysis of only stage I patients, increased Wip1 expression was also significantly associated with a lower overall survival rate (P = 0.023, log–rank test). These results indicate that the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma. (Cancer Sci, 2011; 102: 1101–1106)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rhabdomyosarcoma is a well-known neoplasm in children that frequently occurs in the extremities, the head and neck region, and the genitourinary tract. To the best of our knowledge, pulmonary primary ...rhabdomyosarcoma in adults is exceedingly rare, and few resected cases have been reported. We report a case of pulmonary primary rhabdomyosarcoma that was surgically resected then treated with adjuvant chemotherapy (vincristine, actinomycin-D and cyclophosphamide). At 9 months after surgery, the patient is free from disease. Although the prognosis of rhabdomyosarcoma is unfavorable, surgical resection and adjuvant therapy could be a potential treatment strategy for pulmonary primary rhabdomyosarcoma.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
8.
Reply Nishio, Wataru
The Annals of thoracic surgery,
09/2017, Volume:
104, Issue:
3
Journal Article
A precise preoperative diagnosis of 'very early' lung carcinoma may identify patients who can undergo curative surgery with limited resections.
Data from a multi-institutional project were collected ...on 1737 patients who had undergone limited resections (segmentectomy or wedge resection) for T1N0M0 non-small-cell carcinomas. As it was expected, this study was predominantly including ground glass nodules. Computed tomography was used to obtain the ratio of consolidation to the maximal tumour diameter to determine invasive potential of the tumours. Overall and disease-free survivals and recurrence-free proportions were analysed.
Median age was 64 years. Mean maximal diameter of the tumours was 1.4±0.5 cm. Overall and recurrence-free survivals after limited lung resection were 94.0 and 91.1% at 5 years, respectively. Recurrence-free proportions were 93.7% at 5 years. Unfavourable prognostic factors in overall survival were lymph node metastasis, interstitial pneumonia, male gender, older age, comorbidities (cardiac disease, diabetes etc.) and consolidation/tumour ratio (C/T)≤0.25. C/T≤0.25 predicted good outcomes especially in cT1aN0M0 disease. In a subclass analysis of cT1N0M0 squamous cell carcinomas, wedge resection was the only unfavourable prognostic factor in both overall and disease-free survivals.
If the patient was 75 years old or younger and was judged fit for lobectomy, limited resection for cStage I non-small-cell lung cancer (NSCLC) showed excellent outcomes and was not inferior to the reported results of lobectomy for small-sized NSCLC. The carcinomas with C/T≤0.25 rarely recur and are especially good candidates for limited resection.
Objective
The aim of the study was to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) for detection and subtype classification in pulmonary adenocarcinomas through comparison ...with short TI inversion recovery turbo spin-echo imaging sequence (STIR).
Methods
Thirty-two patients (mean age, 65.2 years) with 33 adenocarcinomas (mean diameter, 27.6 mm) were enrolled in this study. The detection rates of both sequences were compared. The ADC values on DWI and the contrast ratio (CR) between cancer and muscle on STIR were measured and those were compared across subtype classifications. Finally, ROC-based positive tests were performed to differentiate subtype classifications, and differentiation capabilities were compared.
Results
The DWI detection rate 85% (28/33) was significantly lower than that of STIR 100% (33/33),
P
< 0.05. The ADC values showed no significant difference regarding subtype classification; however, the CRs of bronchio-alveolar carcinomas (BACs) were significantly lower than those of other types (
P
< 0.05). When threshold values for differentiating BACs from others were adapted, the sensitivity and accuracy of DWI were significantly lower than those of STIR (
P
< 0.05). For differentiating adenocarcinomas with mixed subtypes from those with no BA component, there were no significant differences between the two sequences.
Conclusion
STIR is more sensitive for detection and subtype classification than DWI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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