Chest
Volume 143, Issue 1, January 2013, Pages 146-151
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Original Research
Lung Cancer
Histologic Assessment of Tumor-Associated CD45+ Cell Numbers Is an Independent Predictor of Prognosis in Small Cell Lung Cancer

https://doi.org/10.1378/chest.12-0681Get rights and content

Background

Small cell lung carcinoma (SCLC) continues to have a poor prognosis, with a 2-year survival of < 20%. Studies have suggested that SCLC may affect the immune system to allow it to evade immunologic responses. We hypothesized that any such effect would be characterized by a decrease in the lymphoid cells associated with the tumor in biopsy specimens and that this might relate to patient outcome.

Methods

Sixty-four SCLC biopsy specimens were immunohistochemically stained with anti-CD45 antibody to identify immune cells associated with the tumor. A mean CD45 count per high-power field for each case was obtained, and the results were correlated with age, sex, stage, performance status (PS), treatment with chemotherapy/radiotherapy, and overall survival.

Results

The median CD45 count for all cases was taken as 40 (CD4540). Kaplan-Meier plots demonstrated better survival for patients with a CD4540 > 40 (P < .009). No relationship between CD4540 and age, sex, stage, or treatment by chemotherapy or radiotherapy was identified. Although PS was a significant predictor of survival (P = .014), it did not correlate with CD4540. In patients with better Eastern Cooperative Oncology Group PS (≤ 2), the CD4540 demonstrated a highly significant survival advantage for those with CD4540 > 40 (P < .0001).

Conclusions

The data indicate that (1) simple immunohistochemical assessment of immune cell infiltrates in routinely processed and stained biopsy specimens of primary tumors can provide prognostic information in SCLC and (2) tumor-associated CD45+ cells in SCLC biopsy specimens may be a good clinical marker to identify patients with poor prognosis despite good PS.

Section snippets

SCLC Cases

Ethical and institutional management approval for the study was obtained (LREC/2004/8/16). Sixty-four biopsy samples with primary lung SCLC from the years 1999 to 2001, for which sufficient residual material was available for study and for which clinical data were available, were identified from the pathology archives at the Royal Infirmary of Edinburgh (Table 1). The cases selected included four resection specimens, 14 core biopsies, 43 bronchial biopsies, and three mediastinal biopsies.

CD45 Counts and Overall Survival

Immunohistochemical staining of the sections highlighted the presence of CD45+ cells within the sections examined (Fig 1). The CD45 counts obtained for the 64 cases had an average of 37.6 positive cells per field, with a range of 2.8 to 127.4. The range and average value for each case counted is shown in Figure 2. Analysis of interobserver variability showed no statistical difference between the mean counts achieved by the observers, and differences in classification of sections as “high” or

Discussion

SCLC is a highly aggressive tumor with a poor prognosis that has frequently widely disseminated by the time of diagnosis. For many years, this type of lung cancer has been recognized as systemically influencing the function of the immune system. Although patients may respond to chemotherapy and/or radiotherapy, overall survival remains poor,4 and subsequent relapse and death are the usual outcome. Predictors of poor outcome and survival have centered on traditional factors, such as the stage of

Conclusions

The number of patients studied is relatively small and the historical data we had available did not include TNM staging, which has been found to provide better prognostic information than previous staging systems for SCLC.25 The data do strongly suggest that this is an area requiring further investigation. Many patients with SCLC clearly have mediastinal and hilar nodal enlargement at presentation. They are now frequently investigated using mediastinal sampling techniques, such as endobronchial

Acknowledgments

Author contributions: Dr Sethi is the guarantor of the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Mr Wang: contributed to the laboratory work, data analysis, editing, and approval of the manuscript.

Dr Hodkinson: contributed to the collection of patient data, laboratory work, data analysis, editing, and approval of the manuscript.

Dr McLaren: contributed to the laboratory work, data analysis, editing, and approval of the manuscript.

Dr

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    Funding/Support: This work was funded by the Medical Research Council (United Kingdom) and the Chief Scientist's Office (Scotland) [Grant CZB/4/504].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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    Drs Wallace and Sethi contributed equally to this work.

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