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Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma.

Abstract
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 HA-positive cancer cells was associated with a shortened disease-free 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 Cox's 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.
AuthorsR Pirinen, R Tammi, M Tammi, P Hirvikoski, J J Parkkinen, R Johansson, J Böhm, S Hollmén, V M Kosma
JournalInternational journal of cancer (Int J Cancer) Vol. 95 Issue 1 Pg. 12-7 (Jan 20 2001) ISSN: 0020-7136 [Print] United States
PMID11241304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2001 Wiley-Liss, Inc.
Chemical References
  • Hyaluronan Receptors
  • Hyaluronic Acid
Topics
  • Adenocarcinoma (metabolism, mortality, therapy)
  • Adult
  • Aged
  • Carcinoma (metabolism, mortality, therapy)
  • Carcinoma, Non-Small-Cell Lung (metabolism, mortality, therapy)
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Hyaluronan Receptors (metabolism)
  • Hyaluronic Acid (biosynthesis)
  • Immunohistochemistry
  • Lung Neoplasms (metabolism, mortality, therapy)
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Recurrence
  • Stromal Cells (metabolism)
  • Treatment Outcome

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