No abstract

Aims-To investigate the expression of catenins ( , , and ) in non-small cell lung carcinoma (NSCLC) and its relation to clinicopathological factors and prognosis. Methods-The expression of catenins was analysed immunohistochemically in 261 patients with resected NSCLC, diagnosed between 1978 and 1996 in eastern Finland. The cell proliferation index of the tumours was analysed by means of an image analyser. The staining results were compared with clinicopathological characteristics and survival. Results-Normal catenin staining was found significantly more often in adenocarcinomas than in squamous cell carcinomas or anaplastic/large cell carcinomas. Reduced staining of -catenin, -catenin, and -catenin was related to poor diVerentiation of the tumour. The tumours with reduced staining of -catenin or -catenin often had higher cell proliferation activity. Nuclear staining of -catenin and -catenin was found in 16 (7%) and 29 (13%) cases, respectively. This nuclear staining correlated directly with increased cell proliferation and inversely with membranous staining. In survival analyses the predictors of overall and disease free survival were stage and tumour type. The expression of catenins did not aVect survival. Conclusions-The expression of -catenin,-catenin, and -catenin is related to histological type and diVerentiation in NSCLC, although catenins have no independent prognostic value. However, this study supports the important role of the nuclear accumulation of -catenin and -catenin in highly proliferative cells. (J Clin Pathol 2001;54:391-395)

The prognostic value of hyaluronan (HA) was analyzed in a large number of patients (n ‫؍‬ 261) with non-small-cell lung cancer (NSCLC) by staining archived tumor samples with a biotinylated HA-specific probe. The level of HA in the tumor cells and surrounding stroma was scored and compared with parallel CD44 stainings, clinicopathological factors and survival data. Adenocarcinomas were characterized by a low percentage of HA-positive cells with low staining intensity compared with squamous-cell and large-cell/anaplastic carcinomas. The HA signal in the peri-tumoral stroma was often higher than that in the uninvolved stroma in all subgroups of NSCLC. CD44 and HA associated with the cancer cells showed a strong positive correlation with each other. In the whole tumor material, dominated by squamous-cell carcinomas (n ‫؍‬ 168), recurrences were more often found in cases showing a low percentage of cancer cell-associated HA. However, within the adenocarcinoma subgroup (n ‫؍‬ 68), a high percentage of cell-associated HA was correlated with poor tumor differentiation. Also specific for the adenocarcinoma subgroup was the increased number of recurrences in cases with a strong stromal HA signal. In survival analysis of the whole material (n ‫؍‬ 189), a low percentage of HApositive cancer cells was associated with a shortened diseasefree survival (DFS) together with stage and tumor type. However, in the subgroup of patients with adenocarcinoma (n ‫؍‬ 49), a strong stromal signal for HA predicted poor DFS. The level of HA in the stroma of adenocarcinomas retained its prognostic value in Coxs multivariate analysis. These results indicate that the frequency and intensity of HA has a significant prognostic value in NSCLC, particularly when the histological subtypes are analyzed as separate entities. © 2001 Wiley-Liss, Inc. Key words: hyaluronan; CD44; extracellular matrix; lung cancer; survivalCell-extracellular matrix interactions participate in several steps required for tumor cell invasion and formation of metastases. 1 These include different cell-adhesion molecules and their ligands. 2 Hyaluronan (HA) is a linear extracellular polysaccharide present in nearly all connective tissues and body fluids of vertebrates, and it is also expressed in several squamous epithelia. It is synthesized on the cytoplasmic side of the plasma membrane, extruded through the membrane and often remains bound to its surface receptor CD44. 3 Previous studies have shown that the level of HA in the tumor stroma correlates with tumor aggressiveness, supporting the hypothesis that HA promotes cell migration and invasion. 4 -6 This has been explained by the highly expanded, hydrated extracellular space provided by HA, which facilitates cell movement, and by HA signaling through its receptors CD44 and RHAMM. 6 Also, degradation products of HA may enhance tumor growth by stimulating malignant neovascularization. 7,8 While most malignant tumors show increased HA signal in the adjacent stroma, the expression of HA in tumor cells depends on the tumor ty...

No abstract

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation, and proliferation, and is supposed to contribute to the spreading of several human cancers. Little is known about the role of HA in the development and progression of differentiated thyroid carcinoma (DTC). The expression and prognostic value of HA were therefore evaluated in 204 consecutive patients with DTC. A biotinylated affinity probe specific for HA was applied to paraffin-embedded tumour samples to assay the expression of HA in carcinoma cells and in intra/peritumoural stroma. In a majority of the samples, a high percentage (>or=90%) of normal thyroid follicle epithelial cells were HA-positive. This high percentage was also found in 80 (47%) papillary carcinomas, but only in seven (21%) follicular carcinomas (p=0.004). Age (>60 years) of the patients was significantly associated with a low percentage of HA-positive cancer cells (p=0.013). Cancer cell-associated HA correlated significantly with the percentage of cells expressing total CD44 and its isoforms containing exons v3 and v6 (r=0.223-0.289, p<0.001 for all). The tumour stroma was always positive for HA. Stromal staining intensity did not differ markedly between papillary and follicular carcinomas. A strong stromal HA staining intensity was related to distant metastases (p=0.044), high pTNM stage (p=0.024), old age (>60 years) (p=0.043), and cancer-related mortality (p=0.001). In a log-rank univariate survival analysis, strong stromal HA staining intensity was related to DTC mortality (p=0.0007). Cancer cell-associated HA expression did not significantly correlate with patient survival. In Cox's multivariate survival analysis, age (>60 years, p=0.0164), gender (p=0.0251), and pTNM stage (p=0.0121) were significant independent prognostic factors for DTC-related death. These results suggest that strong stromal HA staining intensity is related to progression and unfavourable outcome in DTC patients, while the clinical factors remain more powerful in predicting DTC-related death.