Prognostic Significance of a Histologic Subtype in Small Adenocarcinoma of the Lung: The Impact of Nonbronchioloalveolar Carcinoma Components

Sakao, Yukinori; Miyamoto, Hideaki; Sakuraba, Minoru; Oh, Tsumin; Shiomi, Kazu; Sonobe, Satoshi; Izumi, Hiroshi

doi:10.1016/j.athoracsur.2006.07.051

Cited by 69 publications

(69 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As others have shown consistently throughout the literature, 10,34,36,37 our fi ndings demonstrate a biologic difference in the increased rate of adenocarcinomas in never smokers vs current smokers, in general, and BACs, in particular ( Table 1 ). Others also have found on multivariate analysis that BAC is a signifi cant favorable risk factor for overall NSCLC survival.…”

Section: Discussionsupporting

confidence: 63%

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

Meguid¹,

Hooker²,

Harris³

et al. 2010

Chest

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer death in the United States. 1 Although it is well known that lung cancer is associated with tobacco use, it is also apparent that never smokers are susceptible to the disease. Comparisons of genetic and epigenetic aberrations in non-small cell lung cancer (NSCLC) among smokers and never smokers have revealed marked differences in tumor biology that have resulted in clinicopathologic distinctions between smokers and never smokers. Data have established that mutational differences in the active kinase domain of the epidermal growth factor receptor confer increased sensitivities of a subset of never smokers with lung cancer to tyrosine kinase inhibitors. 2,3 Less well established is the actual natural history of NSCLC in never smokers compared with smokers. Emerging tumor biology data, especially recent reports highlighting fewer genomic alterations in never smokers, such as gene Results: Never smokers were signifi cantly more likely than current smokers to be women ( P , .01), older ( P , .01), and to have adenocarcinoma ( P , .01) and bronchioloalveolar carcinoma ( P , .01). No statistically signifi cant differences existed in stage distribution at presentation for the analytic cohort ( P 5 .35) or for the subgroup undergoing surgery ( P 5 .24). The strongest risk factors of mortality among patients with NSCLC who underwent surgery were advanced stage (adjusted hazard ratio, 3.43; 95% CI, 2.32-5.07; P , .01) and elevated American Society of Anesthesiologists classifi cation (adjusted hazard ratio, 2.18; 95% CI, 1.40-3.40; P , .01). The minor trend toward an elevated risk of death on univariate analysis for current vs never smokers in the surgically treated group (hazard ratio, 1.20; 95% CI, 0.98-1.46; P 5 .07) was completely eliminated when the model was adjusted for covariates ( P 5 .97). Conclusions: Our fi ndings suggest that smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal.CHEST 2010; 138(3):500-509Abbreviations: aHR 5 adjusted hazard ratio; AJCC 5 American Joint Commission on Cancer; ASA 5 American Society of Anesthesiologists; BAC 5 bronchioloalveolar carcinoma; HR 5 hazard ratio; NSCLC 5 non-small cell lung cancer

show abstract

Section: Discussionsupporting

confidence: 63%

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

Meguid¹,

Hooker²,

Harris³

et al. 2010

Chest

View full text Add to dashboard Cite

show abstract

“…21,22 However, histological criteria for distinguishing between non-invasive and invasive tumor remain somewhat ambiguous. Microscopic features, such as desmoplasia, disruption of elastic fibers, presence of papillary, or solid tumor structures have been considered as indicators of invasion of lung adenocarcinomas; 8,[23][24][25] however, there is no consensus yet among pathologists as to what should be deemed as the real evidence of invasion.…”

Section: Discussionmentioning

confidence: 99%

“…36 Patients with pure bronchioloalveolar carcinoma or minimally invasive cancer, for example, can be successfully treated with surgery alone. 4,21,22 In this setting, analysis of subepithelial myofibroblasts by a-smooth muscle actin staining might be helpful for identifying a subset of invasive adenocarcinomas requiring no postoperative chemotherapy, ie, tumors with myofibroblast pattern of group I. Conversely, stage I patients with tumors showing myofibroblastic pattern of group III may be treated with postoperative adjuvant therapy, as these patients have a much Subepithelial myofibroblast in lung cancer D Matsubara et al poorer prognosis (5-year survival of 18% compared with 97 and 81% for group I and II, respectively).…”

Section: Discussionmentioning

confidence: 99%

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

et al. 2009

View full text Add to dashboard Cite

We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma and a subset of invasive lung adenocarcinoma. The subepithelial myofibroblasts we describe were observed in a peculiar location beneath the cancer cells in the alveolar septa. Immunohistochemically, they were positive for a-smooth muscle actin and calponin, but negative for desmin and h-caldesmon. To gain insight into their biological significance, we examined 116 surgically resected lung adenocarcinomas. The resected tumors included 13 bronchioloalveolar carcinomas, 20 mixed type adenocarcinomas with bronchioloalveolar carcinoma components, 57 papillary adenocarcinomas, 22 solid adenocarcinomas with mucin, and 4 acinar adenocarcinomas. All specimens were immunostained for a-smooth muscle actin to visualize the myofibroblasts. In all of the pure bronchioloalveolar carcinomas observed, the subepithelial myofibroblasts were completely preserved adjacent to the cancer cells. In mixed adenocarcinomas with bronchioloalveolar carcinoma components, subepithelial myofibroblasts were present in the bronchioloalveolar carcinoma components, but scanty in the invasive areas, where stromal myofibroblasts emerged between the cancer cell nests. Subepithelial myofibroblasts were retained, however, in the invasive areas of a subset of invasive adenocarcinomas. Survival analysis showed that the retention of subepithelial myofibroblasts in these invasive tumors was associated with low rates of lymphatic and vascular invasion, a low rate of lymph node involvement, and an excellent patient survival. These results suggest that subepithelial myofibroblasts increase in bronchioloalveolar carcinomas, but are gradually replaced by typical stromal myofibroblasts during progression into invasive cancer. A subset of invasive adenocarcinomas retains subepithelial myofibroblasts. Analysis of subepithelial myofibroblasts may be helpful in identifying a subset of lung adenocarcinoma with excellent prognosis.

show abstract

“…13,14 In our study 60 of 65 patients were diagnosed with non-BAC adenocarcinomas, whereas only 5 patients showed mixed BAC histology. Most likely, due to the low number of mixed-BAC cases, no impact of the two categories on survival was observed (data not shown).…”

Section: Emmprin Staining Score and Cellular Localizationmentioning

confidence: 93%

“…The patient cohort consisted of 65 patients with adenocarcinoma, 58 patients with squamous cell carcinoma, 15 patients with large cell carcinoma, and 12 patients with mixed histologies. Adenocarcinomas were further differentiated into tumors with and without bronchioalveolar components (mixed BAC and non-BAC, respectively 13,14 ). As only five patients displayed the mixed-BAC phenotype, subgroup analysis was not performed.…”

Section: Patientsmentioning

confidence: 99%

Cellular localization of EMMPRIN predicts prognosis of patients with operable lung adenocarcinoma independent from MMP-2 and MMP-9

et al. 2008

View full text Add to dashboard Cite

Extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN, CD147) is a multifunctional protein that has been implicated in cancer invasion and metastasis by the induction of MMPs. To address its role in primary tumors of human non-small-cell lung cancer we assessed whether EMMPRIN expression is associated with the expression of MMP-2 and MMP-9 and with patient survival. Primary tumors of 150 patients (65 adenocarcinomas, 58 squamous cell carcinomas, and 27 of other subtypes) with completely resected lung cancers were stained by immunohistochemistry. We assessed intensity, extent, and cellular localization of EMMPRIN staining and determined MMP-2 and MMP-9 expression. 145 tumors expressed EMMPRIN (strong expression in 61 tumors), which was predominantly localized at the tumor cell membranes in 102 (68%) patients. We could not determine any correlation between EMMPRIN expression and MMP-2 or MMP-9 expression. The prognostic relevance of EMMPRIN was evaluated by Kaplan-Meier and multivariate Cox regression analysis in patients with adenocarcinoma (n ¼ 57) and squamous cell carcinoma of the lung (n ¼ 56). The median follow-up period was 36.0 months (range 4-156 months). Staining scores for EMMPRIN and MMP-2 and MMP-9 derived from staining intensities and percentages of positive cells did not predict outcome of patients. In contrast, univariate survival analysis demonstrated that membranous localization of EMMPRIN was associated with shortened survival in patients with adenocarcinoma (P ¼ 0.03; log-rank test), but not in squamous cell carcinoma. For the former patients, membranous EMMPRIN expression was also an independent predictor of patient survival (P ¼ 0.04; Cox regression analysis). The findings point to a role of EMMPRIN for the progression of adenocarcinoma of the lung that is unrelated to its function as inducer of MMPs. Modern Pathology (2008) 21, 1130-1138 doi:10.1038/modpathol.2008 published online 20 June 2008 Keywords: extracellular matrix; matrix metalloproteases; lung cancer; survival analysis; prognosis Lung cancer is still the most common cause of cancer-related death in Europe and in the United States 1,2 with non-small-cell lung cancer affecting approximately 80% of all lung cancer patients. 1,3 In stage I, only 60-65% of non-small-cell lung cancer patients, whose tumors were completely resected, are still alive 5 years after surgery. 4,5 This obvious aggressiveness is poorly understood and prompted us to search for potential molecular markers and mechanisms for early systemic spread of nonsmall-cell lung cancer.We previously found that disseminated cancer cells from non-small-cell lung cancer can be detected in bone marrow and lymph nodes and that the detection of such cells is specifically associated with poor survival in early stage patients. Moreover, we observed that one of the most frequently

show abstract

Prognostic Significance of a Histologic Subtype in Small Adenocarcinoma of the Lung: The Impact of Nonbronchioloalveolar Carcinoma Components

Cited by 69 publications

References 12 publications

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

Cellular localization of EMMPRIN predicts prognosis of patients with operable lung adenocarcinoma independent from MMP-2 and MMP-9

Contact Info

Product

Resources

About