Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment

OBJECTIVE: The definition of visceral pleural invasion in lung cancer TNM classification of the International Union Against Cancer lacks detail. The purpose of this study was to evaluate the significance of the extent of pleural involvement as a prognostic factor and to propose a refined TNM classification on the basis of visceral pleural invasion. METHODS: We reviewed 1653 consecutive patients with T1, T2, and T3 surgically resected non-small cell lung cancer for their clinicopathologic characteristics and prognoses. Visceral pleural invasion was classified by using the Japan Lung Cancer Society criteria: p0, tumor with no pleural involvement beyond its elastic layer; p1, tumor extension beyond the elastic layer but no exposure on the pleural surface; and p2, tumor exposure on the pleural surface. RESULTS: The 5-year survivals for patients with p1 or p2 tumors of 3 cm or less were identical and significantly worse than those for patients with p0 tumors of the same size. Patients with p1 or p2 tumors of greater than 3 cm and patients with T3 cancers had essentially identical survivals. CONCLUSIONS: Visceral pleural invasion should be defined as tumor extension beyond the elastic layer of the visceral pleura, regardless of its exposure on the pleural surface. A tumor of 3 cm or less with visceral pleural invasion should remain classified as a T2 tumor, as presently occurs in the International Union Against Cancer staging system, and tumors of greater than 3 cm with visceral pleural invasion should be upgraded to T3 status in the International Union Against Cancer TNM classification.     

Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung

BACKGROUND: The histologic determinants of survival after surgical resection of stage II nonsmall cell lung cancer are poorly understood. We analyzed the prognostic significance of a number of histologic features after complete resection of T1-2N1M0 nonsmall cell cancer of the lung. METHODS: The case notes and histology of all patients who underwent a potentially curative surgical resection for T1-2N1M0 nonsmall cell carcinoma of the lung between 1991 and 1997 were reviewed retrospectively. The following histologic factors were recorded: histologic type of tumor; number of nodes with metastatic deposits together with their nodal station; the presence of vascular invasion, visceral pleural involvement, and cellular necrosis; and grade of tumor. The results from 98 patients were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Univariate analysis showed that only three factors had a statistically significant correlation with a poor prognosis: vascular invasion (p = 0.002), nonsquamous histology (p = 0.005), and visceral pleural involvement (p = 0.002). Multivariate analysis revealed that all three factors were significant independent adverse prognostic indicators. CONCLUSIONS: Visceral pleural involvement, nonsquamous histology, and vascular invasion are all significant adverse prognostic factors after surgical resection of T1-2N1M0 nonsmall cell cancer of the lung. These findings conflict with previously published reports, and we advocate a prospective, large-scale study in order to clarify the prognostic significance of histologic characteristics in stage II disease.     

Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer

OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is considered a poor-prognostic factor, further information is lacking, especially in relation to other clinicopathologic prognostic factors. We assessed the relationship between visceral pleural invasion and other clinicopathologic characteristics and evaluated its significance as a prognostic factor. METHODS: We reviewed 1074 patients with surgically resected T1/2 non-small cell lung cancer for their clinicopathologic characteristics and prognoses. The patients were divided into 2 groups according to visceral pleural invasion status (visceral pleural invasion group and non-visceral pleural invasion group). Both groups were compared with regard to age, sex, histology, tumor size, tumor differentiation, lymph node involvement, lymphatic invasion, vascular invasion, scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level, and survival. Univariate and multivariate analyses were conducted. RESULTS: Visceral pleural invasion was identified in 288 (26.8%) of the resected specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non-visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in the visceral pleural invasion group. The difference between groups was highly significant ( P < .0001). Visceral pleural invasion was also significantly associated with a higher frequency of lymph node involvement. However, regardless of N status (N0 or N1/2), there was a significant difference in survival when the visceral pleura was invaded. Visceral pleural invasion was observed significantly more frequently in tumors with factors indicative of tumor aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion, vascular invasion, high scar grade, high nuclear atypia grade, high mitotic index, and high serum carcinoembryonic antigen level. By multivariate analysis, visceral pleural invasion proved to be a significant independent predictor of poor prognosis in non-small-cell lung cancer patients with or without lymph node involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor-prognostic factor, regardless of N status. Our analyses indicated that visceral pleural invasion is an independent indicator of non-small cell lung cancer invasiveness and aggressiveness.     

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology

BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.     

Loss of heterozygosity of chromosome 16q in gallbladder carcinoma.

BACKGROUND: The present study was planned to investigate cumulative genetic changes during development and progression of gallbladder carcinoma (GBC) in clinical patients. MATERIALS AND METHODS: We examined GBC DNA from resected tissue isolated from 56 cases of GBC for loss of heterozygosity (LOH) at six loci on five chromosomal arms (1p36, 9p21, 13q14, 16q24, 17p13), using highly polymorphic microsatellite markers. RESULTS: High incidences of LOH at 1p36 (19/36: 53%), 9p21 (12/32: 38%), 13q14 (20/36: 56%), 16q24 (31/54: 61%), and 17p13 (15/36: 42%) were detected. When comparing genetic features with clinicopathological stages of these tumors, it appeared that only LOH at 16q24 had a high incidence (5/6: 83%) at an early stage (T1a: tumor invades lamina propria) of the disease, although large numbers of LOH were found on all chromosomal arms in tumors of more advanced stages (T1b, T2, T3, and T4). CONCLUSION: These results suggested that the putative tumor suppressor gene on 16q24 may be strongly related to an early step of carcinogenesis in GBC and that GBC acquires a high malignant potential when the tumor invades the muscle layer.     

Diagnosis of Visceral Pleural Invasion in Resected Lung Cancer Using a Jet Stream of Saline Solution

Background. Visceral pleural invasion by the tumor is an important prognostic factor in patients undergoing resection for lung cancer. We developed a method to detect more accurately the presence of visceral pleural invasion in resected lung cancer.

Methods. The surface of the visceral pleura over 90 resected peripheral tumors was irrigated twice with a jet stream of saline solution using a 20-mL syringe with a 21-gauge needle, and then the fluid, which contained desquamated cells, was collected for cytologic analysis. When cancer cells were found in the collected fluid, the tumor was judged to have invaded the visceral pleura.

Results. Thirty-eight (42%) resected tumors were identified as having visceral pleural invasion either by our new method or by pathologic examination. Twenty-four cases were detected by the jet stream of saline method alone, 5 by pathologic examination alone, and 9 by both techniques. The sensitivity and accuracy of the two approaches in the diagnosis of visceral pleural invasion were 87% and 94%, respectively, for our new method, and 37% and 73%, respectively, for pathologic examination (p < 0.0001). Furthermore, among 38 patients who had a tumor demonstrating visceral pleural invasion, 5 (13%) and 9 (24%) patients, respectively, had cancer cells in the pleural effusion and intrapleural lavage fluid.

Conclusions. Our findings suggest that our method is useful in detecting cancer invasion of the visceral pleura, which is considered one of the causes of malignant effusion.     

Visceral pleural involvement in nonsmall cell lung cancer: prognostic significance

BACKGROUND: A tumor of any size that invades the visceral pleura is classified in the T2 category; however, the definition of the visceral pleural involvement has remained somewhat ambiguous. It is unclear whether the T2 category includes the p2 status alone or incorporates the extent of the p1 status. METHODS: We retrospectively analyzed the survival of 474 patients with T1 and T2 nonsmall cell lung cancer to evaluate the influence of the degree of visceral pleural involvement (p0, p1, and p2) on the prognosis and to clarify the definition of the visceral pleural involvement. RESULTS: The 5-year survival rates according to the degree of visceral pleural involvement were 68.0% in p0 (n = 345), 43.9% in p1 (n = 110), and 54.9% in p2 (n = 19; p0 versus p1, p = 0.0004; p0 versus p2, p = 0.013; and p1 versus p2, p = 0.61). The degree of visceral pleural involvement (p0 versus p1/p2) was a significant independent prognostic factor from tumor size and lymph node involvement, by multivariate analysis (relative risk = 1.47, p = 0.033). The prognosis of pN0 patients with p1 and tumor size 3 cm or less was significantly poorer than that of those with p0 and tumor size 3 cm or less (p = 0.0004), and the prognosis of patients with p1 and tumor size more than 3 cm was significantly poorer than that of those with p0 and tumor size more than 3 cm (p = 0.024). CONCLUSIONS: The degree of visceral pleural involvement (p0 versus p1/p2) is an important component of the lung cancer staging system. Tumors with p1 and p2 status should be regarded as representing visceral pleural involvement and T2 disease.     

Impact of elastic staining on the staging of peripheral lung cancers

Accurate staging of lung cancer has a profound impact on patient management. For stage I nonsmall cell lung carcinomas (NSCLCs), the absence (stage IA) or presence (stage IB) of visceral pleural invasion represents a critical therapeutic branch point: patients with stage IB NSCLC benefit from adjuvant chemotherapy, whereas patients with stage IA NSCLC do not. Elastic staining has been advocated as a simple method for visualizing pleural invasion. The purpose of this study was to determine whether routine elastic staining of the resected peripheral NSCLCs alters tumor staging in a meaningful way. The study cases consisted of 100 consecutive peripheral NSCLCs resections that were pathologically staged as IA based on routine histologic assessment. Each case was stained with the Movats pentachrome elastic stain to aid identification of visceral pleural invasion. To assess current standards of surgical pathology practice, members of the American Association of Directors of Anatomic and Surgical Pathology were asked whether they never, sometimes, or always order elastic stains for peripheral NSCLCs that abut the pleura. Elastic staining resulted in a change of tumor stage from IA to IB in 19 (19%) cases. Of the 49 pathologists that responded to the survey, 25 (51%) never, 14 (29%) sometimes, and 10 (20%) always order an elastic stain for NSCLCs abutting the pleura. Elastic staining is currently not standard surgical pathology practice for the evaluation of peripheral NSCLCs, but it should be. Invasion of the pleura is an elusive finding that is best appreciated with an elastic stain. Our experience suggests that routine elastic tissue staining should be performed as a standard method of assessing pleural involvement for pleural-based nonsmall cell lung carcinomas.     

Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal

BACKGROUND: Despite an early-stage diagnosis, lung cancer presenting with visceral pleura invasion (VPI) or malignant pleural lavage cytology (PLC) has a poor prognosis. The purpose of this study was to correlate VPI to malignant PLC. METHODS: One hundred forty-three consecutive patients scheduled for surgical lung resection having undergone preresectional pleural lavage cytology were reviewed. There were 121 malignant and 22 nonmalignant lesions. All cases were studied by pathology, histology, previous transthoracic puncture, VPI, and presence of pleural lymphatic involvement. RESULTS: PLC was positive (n = 13) or suspected (n = 5) for malignant cells in, respectively, 10.7% and 4.1% of patients with lung cancer. There was no positive PLC in cases of nonmalignant disease. PLC was positive only in pT2 tumors and almost always when the tumor was exposed on the pleural surface, thus possibly exfoliating within the pleural space (12/17 patients, 70.6%; p < 0.01). Positive PLC was obtained whatever the histology but did not appear related to previous transthoracic puncture or involvement of pleural lymphatics by tumor cells. CONCLUSIONS: VPI and positive PLC are linked, and the appearance of tumor cells within the pleural cavity can be explained by tumor desquamation. The role that visceral pleura involvement and parietal pleura reabsorption play in lung cancer is of paramount importance and deserves further research. A better understanding of their relationship could have major implications in the therapeutic management of non-small cell lung cancer.     

Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer

BACKGROUND: Allelic losses on chromosome arms 2q, 3p, 5q, 6q, 7q, 8p, 9p, 10p, 10q, 11p, 11q, 12p, 13q, 16q, 17p, 17q, 18q, and 21q are reportedly associated with progression and/or initiation of prostate cancer. In the present study, we performed a polymerase chain reaction (PCR) analysis of polymorphic microsatellite loci on the human chromosomes 7 and 12p13-12 in prostate cancer tissue to investigate the extent of involvement of these regions, which may contain putative tumor suppressor genes. METHODS: Tissue samples were obtained at autopsy from 17 men who died of hormone-refractory prostate cancer at Chiba University, Japan, and affiliated hospitals between June of 1992 and June of 1995. DNA from normal tumor or metastatic tissue was used as the template for PCR amplification of a set of 16 polymorphic microsatellite loci on human chromosome 7 and 6 loci on the human chromosome region 12p13-12. RESULTS: The frequencies of cases with loss of heterozygosity (LOH) at 7q31.1 were 8% in primary tumor tissue and 11% in metastatic tissue. The frequencies of cases with LOH at 12p13-12 were 12% in primary tumor tissue and 25% in metastatic tumor tissue. CONCLUSIONS: In the present study, the frequencies of LOH at 7q31.1 were lower than in Western patients, suggesting that LOH in this region is not related to progression of prostate cancer in Japanese patients. The frequency of LOH at 12p13-12 was similar to that reported in Western countries, indicating that 12p13-12 may contain a tumor suppressor gene of prostate cancer.     

Prognostic value of visceral pleural invasion in resected non-small cell lung cancer diagnosed by using a jet stream of saline solution

OBJECTIVE: Visceral pleural invasion caused by non-small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis. METHODS: From January 1992 through December 1998, 143 consecutive patients with peripheral non-small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated. RESULTS: Forty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion (P =.004), even patients with stage I disease (P =.02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival (P =.02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses (P =.03), as were sex (P =.03), age (P = 002), and the stage of the disease (P <.0001). CONCLUSIONS: This study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis.     

Risk factors of recurrence in resected stage I non-small cell lung cancer

We reviewed risk factors of recurrence in resected pathological stage I non-small cell lung cancer (I NSCLC). Objective is 229 complete resected I NSCLC in our department. Risk factors of recurrence were carcinoembryonic antigen (CEA), histology, differentiation, lymphatic invasion, blood vessel invasion, pleural invasion and tumor size. By univariate analysis, lymphatic invasion (p=0.009), blood vessel invasion (p=0.008), pleural invasion, p1 (p=0.013), p2 (p=0.001), and tumor size (value of cut off was 2 cm) were significant risk factors of recurrence. By multivariate analysis, blood vessel invasion (p=0.004), pleural invasion (p1 or p2) [p=0.001], were significantly risk factors of recurrence. It was suggested that I NSCLC presenting pathological blood vessel invasion and/or pleural invasion should be recognized as cases with a high risk of recurrence, and a strict follow-up and adjuvant therapy should be in consideration.     

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.

     

Vascular Endothelial Growth Factor Expression in Stage I Non-Small Cell Lung Cancer Correlates With Neoangiogenesis and a Poor Prognosis

Background: Vascular endothelial growth factor (VEGF) plays an important role in tumor growth and metastasis. We investigated the prognostic significance of VEGF overexpression, intratumoral microvessel density (MVD), and angiolymphatic invasion in stage Ia-b non-small cell lung cancer (NSCLC).Methods: Eighty-five patients undergoing complete surgical resection of pathologic stage Ia-b NSCLC were evaluated. The mean and median clinical follow-up were 37.1 and 39.0 months (range, 30–44 months), respectively. Paraffin-embedded tumor specimens were stained with VEGF and CD31 (a specific endothelial marker) using immunohistochemical methods. VEGF staining was evaluated, by combining both percentage of positive tumor cells and staining intensity, as low (negative and < 20% of tumor cells showing weak positivity), or high (>20% of tumor cells showing strong positivity). CD31 staining was expressed as MVD per high power field at 400× magnification. Angiolymphatic invasion was expressed as either presence or absence.Results: Low VEGF expression was seen in 25 (29%) patients, and high VEGF expression was seen in 60 (71%) patients. The survival rate in patients with low VEGF expression was significantly higher (80%) than that in those with high VEGF expression (48%, P = .018). The mean MVD in the low VEGF group was 23.7 ± 5.7 vs. 34.4 ± 9.3 in the high VEGF group (P = .001). Patients with high MVD also had a significantly lower survival rate than did those with low MVD count (46% vs. 73%, P = .0053). Age, sex, tumor type, and tumor differentiation were not found to be associated with overall survival. The presence of angiolymphatic invasion and T2 stage (i.e., tumor size > 3 cm) were associated with decreased survival. High VEGF expression, tumor size, and angiolymphatic invasion emerged as three independent factors predicting worsening prognosis using multivariate analysis.Conclusion: High VEGF expression within stage I NSCLC is closely associated with high intratumoral angiogenesis and poor prognosis. Immunohistochemical evaluation of T stage and VEGF expression along with examination of angiolymphatic invasion perioperatively may aid in predicting prognosis. Adjuvant therapies aimed at retarding tumor angiogenesis may be considered for stage I NSCLC patients with high VEGF levels.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16-19, 2000.     

Prognostic significance of cyclin D1 expression in resected stage I, II non-small cell lung cancer in Arabs

The aim of this study was to evaluate the prognostic significance of cyclin D1 expression in primary, resected stage I and II non-small cell lung cancer (NSCLC) in Arabs. A longitudinal cohort study of 98 consecutive patients with resected stage I and II NSCLC were evaluated immunohistochemically for the expression of cyclin D1 and determined its prognostic significance by comparison with follow-up data from January 1994 to December 1999. This study included 76 male and 22 female patients. They represented 31 stage I NSCLC and 67 stage II tumors. Expression of cyclin D1 was detected immunohistochemically in 48 (49%) of the 98 NSCLC. Cyclin D1 expression had significantly higher positive results in patients with chronic obstructive pulmonary disease (P=0.001), poorly differentiated carcinoma (P=0.001), presence of vascular invasion (P=0.003), and visceral pleural invasion (P=0.005). Patients with cyclin D1-positive tumors had shorter survival than those with cyclin D1-negative tumors (5-year survival rates, 48% and 74%, respectively; P=0.006 by the log-rank test). In conclusion, a higher percentage of NSCLC with visceral pleural invasion, vascular invasion, poor differentiation of the tumor, patients with chronic obstructive pulmonary disease have positive cyclin D1 expression than other lung tumors.     

Loss of heterozygosity analysis identifies genetic abnormalities in mycosis fungoides and specific loci associated with disease progression

Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.     

Allelic loss on chromosomes 8 and 9 correlates with clinical outcome in locally advanced clear cell carcinoma of the kidney

PURPOSE: We correlated allelic loss on chromosomes 8p, 9p and 14q with clinical outcome in locally advanced conventional renal cell carcinoma. MATERIALS AND METHODS: We analyzed radical nephrectomy specimens from 72 stage P3N0 conventional renal cell carcinomas by microsatellite loss of heterozygosity (LOH) analyses directed at chromosomes 3p, 8p, 9p and 14q (2 primers per chromosome). All patients were treated with surgery only. LOH results were correlated with disease-free survival using the Kaplan-Meier method. RESULTS: We detected LOH on chromosome 3p in 60 of 64 (94%), on chromosome 8p in 19 of 59 (32%), on 9p in 21 of 67 (31%) and on 14q in 18 of 70 (26%) informative cases. Of the 72 patients 24 (33%) had recurrence during followup. On univariate analysis patients with tumors demonstrating LOH on chromosomes 8p and 9q were at high risk for recurrence (p = 0.01). The correlation of recurrence with LOH approached significance for the individual chromosomes 8p and 9p (p = 0.10 and 0.14, respectively). No correlation was observed of LOH on chromosome 14q with recurrence (p = 0.42). The correlation of tumor grade with risk of relapse also approached significance (p = 0.12). On multivariate analysis LOH on chromosome 8p was a more powerful predictor of recurrence than tumor grade. When combinations of LOH on chromosomes were tested, LOH on chromosomes 8p and 9p was the most powerful predictor of recurrence (p = 0.006). CONCLUSIONS: LOH on chromosomes 8p or 9p may provide prognostic significance in patients with locally advanced renal cell carcinoma.     

The Significance of Visceral Pleural Surface Invasion in 321 Cases of Non-Small Cell Lung Cancers with Pleural Retraction

Background

In order to improve prognostic applications and treatment decisions, we report our experiences of visceral pleural surface invasion (VPSI) in non-small cell lung cancers (NSCLCs) with pleural retraction.

Methods

A total of 321 NSCLCs with pleural retraction were identified by carefully inspecting surgically resected specimens. The extent of pleural invasion, including the use of elastic stain, was evaluated. Patients with and without VPSI were compared for clinicopathologic parameters and survival.

Results

VPSI was identified in 170 (53.0?%) of the stage I?CIII cases and 98 (43.4?%) of the patients with stage I disease. VPSI was associated with a higher frequency of tumor size greater than 3?cm, moderate/poor differentiation, vascular invasion, mediastinal lymph node metastasis, extranodal involvement, and higher TNM stages. Multivariate analysis revealed VPSI to be a significant independent predictor of unfavorable prognosis. The 5-year survival of patients with and without VPSI was 57.9 and 83.0?%, respectively (P?=?0.001), and was 74.3 and 88.5?% (P?=?0.005) in stages I?CIII and stage I disease, respectively.

Conclusions

VPSI is an independent factor for poor prognosis in NSCLCs, regardless of lymph node status. Stage IB NSCLCs with PL1 pleural invasion are associated with a survival rate similar to that of stage IA NSCLCs and could be classified as T1 lesions. While surgical treatment is adequate in these patients, stage IB NSCLCs with VPSI have poor prognosis, and these patients should be considered for adjuvant chemotherapy.     

Genetic profile of cumulative mutational damage associated with early pulmonary adenocarcinoma: bronchioloalveolar carcinoma vs. stage I invasive adenocarcinoma

To detect the possible genetic alterations characteristic of bronchioloalveolar carcinoma (BAC) and to study molecular genetic factors responsible for determining the biologic aggressiveness of pulmonary adenocarcinoma, comparative analysis of loss of heterozygosity (LOH) on 9 chromosomal regions was performed in 14 BACs and in 20 stage I adenocarcinomas (AD). The most frequently affected chromosome regions in BAC were 8q and 17p. In stage I AD, more than 60% of the cases showed LOH of 1p, 3p, 5q, 7q, 17p, and 18q loci, and LOH of 1p, 3p, 7q, and 18q was observed with greater frequency than in BAC (P < 0.05). Fractional allele loss (FAL) was significantly greater in stage I AD than in BAC (P < 0.001). In cases with microdissection of multiple sites, intratumoral heterogeneity of LOH status was observed in 73% of BAC and 94% of stage I AD, and homogeneous distribution of LOH of 9p was unique to BAC. The high FAL value was associated with a poor prognosis of BAC, but this trend did not reach statistical significance (P = 0.098). In stage I AD, no correlation was found between LOH of particular chromosomal region or FAL and clinical outcome. LOH of 1p, 3p, 7q, and 18q was associated with invasive properties of pulmonary AD and may be useful in identifying invasive adenocarcinoma when conventional histomorphological tools are not helpful.     

Loss of heterozygosity on chromosomes 10 and 17 in clinically localized prostate carcinoma

Loss of heterozygosity (LOH) at chromosomal loci has been associated with the presence of tumor suppressor genes at the deleted loci. Twenty-six clinically localized, Stage B prostate carcinomas were analyzed for LOH on chromosomes 10 and 17 using microsatellite markers. Two of 26 carcinomas showed LOH on 17p while one showed LOH on 17q. Chromosome 10 showed a complex pattern of LOH with monosomy (1 case), LOH on 10p (1 case), proximal 10q (1 case) and distal 10q (2 cases). Overall 29% of informative cases showed LOH on chromosome 10. These results are consistent with the presence of a tumor suppressor for prostate cancer on 17p and multiple tumor suppressor genes on chromosome 10. © 1996 Wiley-Liss, Inc.