The role of pulmonary resection in tumors metastatic from esophageal carcinoma.

OBJECTIVE: The purposes of this study were to determine the role of surgical treatment and to identify factors affecting survival of patients undergoing resection of pulmonary metastatic tumors from esophageal carcinoma. METHODS: We reviewed 33 patients who had undergone resection of pulmonary metastatic tumors from esophageal carcinoma after definitive treatment. RESULTS: The operative morbidity rate was only 5%, no patients died within 30 days after resection, and complete resection was achieved in 30 patients. The overall 1-, 3- and 5-year survival rates after pulmonary metastasectomy were 79.4, 47.8 and 43.0%, respectively, and the median survival time was 17.9 months. The factors found on univariate analysis to affect survival significantly were disease-free interval <16 months and nodal involvement of the primary tumor. The most frequent pattern of initial recurrence after pulmonary resection was distant metastasis (70%). CONCLUSIONS: We demonstrated the safety and effectiveness of surgical resection for selected patients with pulmonary metastatic tumors from esophageal carcinoma. However, with a high recurrence rate in patients with negative prognostic factors, adjuvant systemic chemotherapy after pulmonary resection should be considered.

Limited resection for early-stage non-small cell lung cancer as function-preserving radical surgery: a review.

Since 'radical lobectomy' was reported by Cahan in 1960, the standard surgical care for lung cancer has been lobectomy, in which units of the lobe are excised with their specific regional hilar and mediastinal lymphatics. However, pulmonary function-preserving limited resection for lung cancer has gradually become more prevalent in the late 20th century. In 1995, Ginsberg et al. conducted a randomized controlled trial in which limited resection (segmentectomy and wide-wedge resection) and lobectomy for stage I lung cancer were compared and reported that limited resection should not be applied to healthy patients with clinical stage IA lung cancer. The detection of small-sized and early-stage lung cancers has improved with advancement in diagnostic technology. Ground-glass opacity of lung nodules, as recognized on thin-slice computed tomography, has also been widely recognized as being correlated with less-invasive pathological findings of alveolar epithelial cell replacement of cancer cells. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group conducted a cohort study of early peripheral lung cancer and investigated the validity thin-slice computed tomography criteria to diagnose non-invasive lung adenocarcinoma for the preoperative prediction of pathological non-invasive cancer. Following this observational study, the on-going JCOG0802/WJOG4607L, JCOG0804/WJOG4507L and JCOG1211 trials were initiated to confirm the validity of limited resection for stage I lung cancer patients stratified according to preoperative thin-slice computed tomography findings; these trials will clarify whether limited resection for lung cancer is not function-preserving but also only curative surgery.

Is cancer history really an exclusion criterion for clinical trial of lung cancer? Influence of gastrointestinal tract cancer history on the outcomes of lung cancer surgery.

Objective: Exclusion of patients with a history of other cancer treatment except in situ situation has been considered to be inevitable for clinical trials investigating survival outcome. However, there have been few reports confirming these influences on surgical outcome of lung cancer patients ever. Methods: Multi-institutional, individual data from patients with non­small cell lung cancer resected between 2000 and 2013 were collected. The patients were divided into two groups: those with a history of gastrointestinal tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of gastrointestinal tract cancer stage, disease-free interval, and treatment method for gastrointestinal tract cancer on the surgical outcome of non­small cell lung cancer was examined. Results: We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of gastrointestinal tract cancer did not affect overall survival or recurrence-free survival. Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels and advanced clinical stage of non­small cell lung cancer. The two groups in the matched cohort demonstrated equivalent overall survival and recurrence-free survival, even in patients with clinical stage I. Gastrointestinal tract cancer stage, disease-free interval and treatment method for gastrointestinal tract cancer were not associated with outcomes. Conclusions: History of early gastrointestinal tract cancer completely resected is not always necessary for exclusion criteria in clinical trial of lung cancer.

A Phase II Study of Partial and Subtotal Thymectomy for Thymoma (JART02).

BACKGROUND: We believe the merit of preservation of a part of the thymus following surgery for thymoma. We evaluated the efficacy of partial or subtotal thymectomy for early-stage thymoma in the prospective study. METHODS: The Japanese Association for Research on the Thymus conducted a multiple institutional study of thymectomy for thymoma localized in the thymus without total thymectomy. Patients without autoimmune disease who had an anterior mediastinal tumor that had been clinically diagnosed as an early-stage thymoma were enrolled in the study. Patients who were positive for anti-acetylcholine receptor antibodies were excluded. RESULTS: Sixty-three patients were enrolled preoperatively; 27 patients were judged as being inappropriate based on the other thymic pathologies or tumor invasion. The remaining 36 cases were diagnosed as early-staged thymoma and analyzed. The mean age of the patients was 61 years. The mean maximal tumor diameter in the resected specimens was 3.6 cm. The most common pathological types of thymoma were AB (n = 10) and B1 (n = 10). The Masaoka stages were classified as stage I (n = 22) and II (n = 14). The mean observation period was 63 months. Two patients died due to respiratory dysfunction, which was not related to thymoma. One hundred percent of the patients remained recurrence-free. CONCLUSIONS: This prospective study suggested the efficacy of partial or subtotal thymectomy for early-stage thymoma in patients without any apparent evidence of autoimmune disease. We can preserve a part of the thymus even following surgery for thymoma to prepare the possible second malignancies or diseases in future.

Histology is a Prognostic Indicator After Pulmonary Metastasectomy from Renal Cell Carcinoma.

OBJECTIVES: There are only a few detailed reports concerning the prognosticators following surgical resection of pulmonary metastases (PMs) from renal cell carcinoma (RCC). We investigated the prognosis of patients with RCC PMs undergoing pulmonary metastasectomy and identified prognostic factors in a multi-institutional retrospective study. METHODS: We retrospectively evaluated 84 patients who underwent resection of PMs from RCC between 1993 and 2014. We assessed the clinicopathological characteristics, focusing on the histological findings of PMs. We classified the histology into three types: pure clear cell carcinoma (N = 68), clear cell carcinoma combined with other histology type (N = 8), and non-clear cell carcinoma (N = 8). We examined the relationship between these histological types and the prognosis of patients with PMs from RCC. RESULTS: Complete resection was achieved in 78 patients (93%). The 5-year overall survival rate after metastasectomy was 59.7%. In multivariate analysis, three factors were found to be independent favorable prognostic factors of overall survival after lung metastasectomy [tumor size <2 cm, hazard ratio (HR) = 0.31, 95% confidence interval (CI) 0.13-0.78, P = 0.012; clear cell type, HR = 0.37, 95% CI 0.16-0.83, P = 0.025; and complete resection, HR = 0.27, 95% CI 0.10-0.78, P = 0.015]. CONCLUSIONS: This study indicates that a histological finding of the clear cell type is a significant favorable prognostic factor in addition to complete resection and a tumor size <2 cm. Histological evaluation of PM lesions is important for predicting survival after metastasectomy.

Thin-section computed tomography findings of lung adenocarcinoma with inherent metastatic potential.

PURPOSE: The solid component of lung ground-glass nodules on thin-section computed tomography (TSCT) reflects cancer cell progression and invasiveness. The purpose of this study was to clarify the cut-off value of preoperative TSCT findings in treating a lesion suspected of being adenocarcinoma and to recognize the timing of surgical resection for lung nodules. METHODS: We reevaluated the TSCT findings in 392 patients with clinical stage IA lung adenocarcinoma who underwent surgical resection between 2003 and 2007. We identified the clinical parameters that were most useful for predicting recurrence and identified a cut-off level for each parameter. RESULTS: Recurrence was observed in 75 (19 %) of 392 patients (median follow-up: 7 years). The size of internal consolidation of a lung nodule (SCL) and the ratio of the SCL to the maximum tumor diameter (C/T ratio) were extracted as independent factors that predicted recurrence. Only 1 (0.3 %) patient each with a lung nodule C/T ratio ≤0.5 and SCL ≤10 mm recurred. These conditions were associated with a significantly better overall survival and recurrence-free survival. CONCLUSION: In patients with clinical stage I lung adenocarcinoma with a C/T ratio ≤0.5 and/or SCL ≤10 mm on TSCT, surgery is extremely likely to achieve a cure.

The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology.

OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

Limited resection trial for pulmonary ground-glass opacity nodules: case selection based on high-resolution computed tomography-interim results.

OBJECTIVE: Our previous trial for small ground-glass opacity nodule on high-resolution computed tomography suggested all these cancers might have been radically managed with limited resection. Good correlation between radiologic and pathologic findings in early lung adenocarcinomas has been reported. We aimed to confirm limited resection efficacy as radical surgery in patients with high-resolution computed tomography-indicated minimally invasive lung cancer. The purpose of this interim analysis is to report the details of the patient and nodule characteristics, intraoperative cytology capability as a negative margin indicator, and patient outcome with the median follow-up period of 7 years and 4 months. METHODS: Enrollment required patients with a tumor ≤2 cm, diagnosed or suspected as a cT1N0M0 carcinoma in the lung periphery and depicted on high-resolution computed tomography as a sub-solid nodule with tumor disappearance ratio ≥0.5. We performed a wedge or segmental resection as appropriate. The primary endpoint is 10 year local recurrence-free survival rate. RESULTS: This study started in November 2003, and 101 patients were enrolled as of November 2009. Of them, 95 were eligible for analysis. There were 38 men and 57 women, aged 30-75, averaging 62 years. Tumor sizes ranged from 7 to 20 mm on computed tomography, averaging 15 mm. There were 11 Noguchi type A tumors, 54 type B tumors, 24 type C tumors, one malignant lymphoma and 5 non-cancerous lesions. All cancers showed no vessel invasion. With a median follow-up period of 88 months, there have been no recurrences. CONCLUSION: So far, high-resolution computed tomography appears to predict non- or minimally invasive ground-glass opacity lung cancers with high reliability, warranting limited resection as curative surgery in this cohort.

Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma.

Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial-mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.

Prognostic impact of microscopic vessel invasion and visceral pleural invasion in non-small cell lung cancer: a retrospective analysis of 2657 patients.

OBJECTIVE: We aimed to assess the prognostic significance of microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) in non-small cell lung cancer (NSCLC). BACKGROUND: VPI is included in the current tumor-node-metastasis (TNM) classification in NSCLC; however, MVI is not incorporated in TNM classification. METHODS: From August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection. In addition to conventional staging factors, we evaluated MVI histologically and analyzed its significance in NSCLC recurrence prognosis. The recurrence-free period in several NSCLC subgroups was analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS: The proportion of patients with a 5-year recurrence-free period was 52.6% and 87.5%, respectively, in those with and without MVI (P < 0.001). Multivariate analysis showed that MVI, similarly to VPI, was found to be an independently significant predictor of recurrence [hazard ratio (HR): 2.78]. In particular, MVI and VPI were the 2 strongest significant independent predictors of recurrence in 1601 patients with pathological stage I disease treated without adjuvant chemotherapy (HR: 2.74 and 1.84, respectively). In each T subgroup analysis, evident and significant separation of the recurrence-free proportion curves were observed among the 3 groups (VPI and MVI absent, VPI or MVI present, and VPI and MVI present). CONCLUSIONS: This study demonstrated that MVI was a significant independent risk factor for recurrence in patients with a resected T1-4N0-2M0 NSCLC. Further data on MVI prognostic impact should be collected for the next revision of the TNM staging system.

Surgical outcomes after initial surgery for clinical single-station N2 non-small-cell lung cancer.

OBJECTIVE: Single-station N2 (Stage IIIA) non-small-cell lung cancer has been reported to have a relatively favorable prognosis after surgery. However, most previous studies examined surgical outcomes in N2 disease by pathologic nodal status but not by clinical nodal status. The objective of this study was to clarify the surgical outcomes in clinical single-station N2 non-small-cell lung cancer patients. METHODS: A total of 125 consecutive patients with clinical single-station N2 non-small-cell lung cancer were treated in our institution between 1992 and 2008. Among them, 97 (78%) patients underwent thoracotomy, and were included in this retrospective study. We defined clinical single-station N2 node as a node measuring 1-2 cm in a single mediastinal station observed on contrast-enhanced computed tomography. The median follow-up period was 5.9 years (range, 1.8-12.6). RESULTS: Eighty-eight (91%) patients underwent lung resection. Of them, 17 (19%) had true (pathologic) single-station N2 disease. Twenty-eight (32%) had pathologic multistation N2 and 43 (49%) had pN0-1 disease with favorable prognoses. The overall survival of the clinical single-station N2/pathologic N2 patients after initial surgery was unsatisfactory with a 5-year overall survival of 23.6%, but their prognoses were heterogeneous. True single-station pathologic N2 status (hazard ratio = 0.35, P = 0.008) and negative subcarinal node status (hazard ratio = 0.34, P = 0.022) were independent favorable prognostic factors after initial resection for clinical single-station N2/ pathologic N2 patients. The patients with both factors revealed a relatively favorable 5-year overall survival of 43.8%. CONCLUSION: Clinical single-station N2 status does not always correspond with pathologic true N2 status. From a prognostic point of view, initial surgery for clinical single-station N2 patients is indicated if their true single-station N2 status and negative subcarinal involvement are preoperatively confirmed.

Tumor-size-based morphological features of metastatic lymph node tumors from primary lung adenocarcinoma.

Most primary lung adenocarcinomas show histological diversity, however, histological diversity in the metastatic lymph node tumors (LNT) is not well defined. The aim of this study was to explore the histological characteristics of the metastatic LNT based on their sizes. We analyzed 163 primary tumors and 509 metastatic LNTs. When the primary tumor showed papillary-predominant subtype, the most frequent histological subtype in the metastatic LNT that were ≤2 mm in diameter was solid subtype (49%), followed by papillary subtype (35%); on the other hand, in the metastatic LNT measuring >2 mm in size, the frequency of tumors showing papillary-predominant subtype increased significantly to 52% (P = 0.04). When the primary tumor showed acinar-predominant subtype, the most predominant subtype in the ≤2 mm metastatic LN tumors was acinar subtype (55%), followed by solid subtype (40%), with the frequency of acinar subtype increasing significantly to 76% in the metastatic LNT that were >2 mm in diameter (P = 0.04). These results indicate that solid subtype is the characteristic histological subtype in the early phase of the LN metastatic process, and that as the metastatic LNT grow larger, they develop morphological features resembling those in the primary tumor.

Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma.

Recently, an association between tumor infiltrating Forkhead box P3 regulatory T cells (Treg ) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of Treg induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between Treg and patient outcome and to investigate whether Treg induction is influenced by the characteristics of cancer-associated fibroblasts (CAF) in lung adenocarcinoma. The numbers of Treg in both the tumor stroma and the tumor nest were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAF influence Treg induction, we selected and cultured CAF from low Treg and high Treg adenocarcinoma. The number of Treg was much higher in the stroma than in the nest (P < 0.01). Patients with high Treg had a significantly poorer prognosis than those with low Treg (overall survival: P = 0.03; recurrence-free survival: P = 0.02; 5-year overall survival: 85.4% vs 93.0%). Compared with the CAF from low Treg adenocarcinoma, culture supernatant of the CAF from high Treg adenocarcinoma induced more Treg (P = 0.01). Also, CAF from high Treg adenocarcinoma expressed significantly higher mRNA levels of transforming growth factor-ß (P = 0.01) and vascular endothelial growth factor (P = 0.01), both of which are involved in Treg induction. Our studies suggest the possibility that CAF expressing immunoregulatory cytokines may induce Treg in the stroma, creating a tumor-promoting microenvironment in lung adenocarcinoma that leads to a poor outcome.

Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma.

Histological vascular invasion (VI) by tumors is reportedly a risk factor influencing recurrence or survival after surgical treatment; however, few studies have evaluated which VI features affect recurrence or survival. The objective of this study was to evaluate how VI features affect recurrence in lung adenocarcinoma patients. We selected 106 patients with pathological stage I lung adenocarcinoma who showed VI and examined the properties of intravascular tumors associated with recurrence. First we investigated the relationship between the frequency of VI in a histological cross-section and the incidence of recurrence; however, a significant impact was not observed. Microscopic examination revealed the intravascular tumors were composed of not only cancer cells but also non-cancerous cells. To examine whether the characteristics of intravascular cancer cells and/or non-cancerous cells have prognostic value, we examined the expression levels of epithelial-mesenchymal transition-related markers in cancer cells and the numbers of infiltrating non-cancerous cells, including macrophages, endothelial cells, and fibroblasts. High levels of E-cadherin expression in the intravascular cancer cells were significant predictors of recurrence (P = 0.004), whereas the expressions of CD44, CD44 variant 6, and vimentin were not. Large numbers of intravascular CD204(+) macrophages (P = 0.016), CD34(+) microvessels (P = 0.007), and α-smooth muscle actin (+) fibroblasts (P = 0.033) were also significant predictors of recurrence. Our results indicated VI with abundant stromal cell infiltrates might be a predictor of recurrence and suggested the tumor microenvironment created by cancer cells and stromal cells within the blood vessel may play an important role during the metastatic process.

Morphophenotypic characteristics of intralymphatic cancer and stromal cells susceptible to lymphogenic metastasis.

The intravessel microenvironment has significant effects on cancer metastasis. The aim of the present study was to determine how the morphologic and immunophenotypic features of cancer cells and infiltrating stromal cells within the permeated lymphatic vessels are associated with lymphogenic metastasis. A total of 137 primary lung adenocarcinoma patients with extratumoral lymphatic permeations were examined. Morphologically, the floating cancer nests within the permeated lymphatic vessels were divided into two types: Type A, consisting of a single large cancer nest; and Type B, consisting of multiple small cancer nests. We compared the clinicopathologic characteristics and the immunophenotypes of the cancer cells and infiltrating stromal cells between the Type A and Type B nests. Eleven of 54 Type A patients (20%) had intrapulmonary metastases, compared with 36 of 83 Type B patients (43%; P = 0.006). Immunohistochemically, Type B cancer cells expressed significantly higher levels of CD44 than Type A cancer cells (mean scoresAUTHOR: Scores - what is this score? Is it the number of cells expressing CD44 or the concentration of CD44 or some other type of scoring system? 43.0 vs 20.5, respectively) and E-cadherin (60.5 vs 31.5, respectively), but lower levels of Geminin (11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%AUTHOR: 11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%, - what do the percentages here refer to? The number of cells expressing geminin and caspase 3? The levels of these factors? Please clarify., respectively). Moreover, a significantly larger number of CD204-positive macrophages were present within the cancer-permeated lymphatic vessels in Type B patients than in Type A patients (mean number 9.5 vs 4.6, respectively). The present study reveals that intralymphatic cancer cell and stromal cell phenotypes are susceptible to lymphogenic metastasis, suggesting that lymphogenic metastasis may be affected by the intralymphatic microenvironment they create.

Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear. METHODS: We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions. RESULTS: Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007). CONCLUSIONS: Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients.

Characteristic immunophenotype of solid subtype component in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components. METHODS: We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results. RESULTS: Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P < 0.001, P < 0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor. CONCLUSIONS: This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.

Differences between squamous cell carcinoma and adenocarcinoma of the lung: are adenocarcinoma and squamous cell carcinoma prognostically equal?

OBJECTIVE: We analyzed pulmonary squamous cell carcinoma and adenocarcinoma patient survival in our single institution database, to evaluate the relationship of histologic analysis to survival and tumor aggressiveness. METHODS: We reviewed 1856 consecutive patients with surgically resected pulmonary squamous cell carcinoma or adenocarcinoma regarding their clinicopathologic characteristics, overall survival and recurrence-free proportion. RESULTS: In squamous cell carcinoma patients, there were more elderly male smokers and more patients with T2-4 tumors, moderately/poorly differentiated tumors, lymph node metastasis or vascular invasion than in adenocarcinoma patients. In all patients and in pN0 patients, patients with squamous cell carcinoma showed significantly poorer overall survival than those with adenocarcinoma, but there were no statistically significant differences in the recurrence-free proportion between the two histologic types. There were statistically significantly more lung cancer-specific deaths in patients with adenocarcinoma than in patients with squamous cell carcinoma (P= 0.001). CONCLUSIONS: There were no differences in the development of recurrence between squamous cell carcinoma and adenocarcinoma of the lung, but considerable differences in overall survival were observed between the two histologic types. According to the stage grouping strategy of the TNM Classification for Lung and Pleural Tumours, these two histologic types need to be staged differently. This survival difference, however, may reflect the difference in patient background rather than in biologic aggressiveness between the two histologic types.

The recurrence of malignant pleural mesothelioma 14 years after extrapleural pneumonectomy: possible histological transformation.

A 56-year-old man underwent extrapleural pneumonectomy for malignant pleural mesothelioma (MPM). The histological diagnosis was epithelioid mesothelioma with T2N0M0, and no sarcomatoid component was observed. Subsequently, 14 years after complete resection, screening computed tomography detected a rapidly growing right thoracic mass, which was diagnosed as a recurrence of MPM on resection. However, it was composed of both epithelioid (50%) and sarcomatoid (50%) components, suggesting possible histological transformation. Although there have been some previous reports on the recurrence of MPM, to the best of our knowledge, this is the first clinical case which indicated that histological transformation of MPM might occur.