Expression of Chemokine Receptor CCR6 as a Molecular Determinant of Adrenal Metastatic Relapse in Patients With Primary Lung Cancer

Christophe M. Raynaud; Olaf Mercier; Philippe Dartevelle; Frédéric Commo; Ken André Olaussen; Vincent de Montpreville; Fabrice André; Laure Sabatier; Jean-Charles Soria

Disclosures

Clin Lung Cancer. 2010;11(3):187-191. 

In This Article

Results

Clinical and Pathologic Features

The characteristics of the 21 patients are described in Table 1. The median age of patients during their initial surgery was 53 years (range, 42–42 years). Patients consisted of 17 men and 4 women. A diagnosis of adrenal metastasis was synchronous with a diagnosis of NSCLC in 5 patients (23.8%) and was metachronous in 16 patients (76.2%). The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5–5.1 months).

Chemokine Receptor Expression Pattern

The CXCR4 receptor was poorly expressed in both primary and adrenal metastases, with only a few cases demonstrating expression. Only 2 primary lung tumors and 3 adrenal metastases exhibited positive CXCR4 staining. Moreover, 2 patients expressed CXCR4 in both their primary and adrenal metastases. Regarding CX3CR1, both primary and adrenal metastases displayed low levels of expression. In contrast, CCR7 was strongly expressed in both primary and adrenal metastases. However, for these 3 chemokines, a percentile analysis demonstrated no drastic difference in expression patterns between primary and adrenal metastases (Figures 1 and 2).

Figure 1.

Visualizations of Chemokine H-Scores in Primary Lung Tumors and Corresponding Adrenal Metastases
Y-axes represent H-scores (percent × intensity), and X-axes represent percentiles of ordered H-scores Fn(x). Only CCR6 presents significant differences in expression between lung and adrenal tumors, with stronger expression in adrenal tumors.

Figure 2.

Representative Images of Staining in Lung Primary Tumors and Paired Adrenal Metastases for CCR6, CCL20, CCR7, CX3CR1, and CXCR4
Magnification of samples, × 400.

On the other hand, CCR6 was far better expressed in adrenal metastases compared with primary lung tumors. Wilcoxon analysis indicated a statistically significant difference in scores of expression between primary and metastatic tumors (P < .0005; Figures 1 and 3).

Figure 3.

CCR6 Scores According to Anatomic Site (Primary Tumors Versus Metastases)
The score is calculated as intensity multiplied by percentage of stained cells. The top of each box represents the 75% quartile (q75); the lower limit of each box is the 25% quartile (q25). The black line inside each box is the median value. The horizontal lines outside of the boxes represent 1.5 times the distance of (q75-q25) from the median value. The formula used is w = median +/-1.5(q75-q25). The small open diamond represents the sole outlier value in the data.

CCL20 Expression in Adrenal Metastases

The expression levels of CCL20 were also assessed in both primary tumors and adrenal metastases. Surprisingly, unlike CCR6, CCL20 was not statistically more often expressed in adrenal tumors compared with corresponding primary lung tumors, even if a trend was evident (P = .1465). Moreover, the expression of CCL20 was assessed in normal tissue, when available, adjacent to adrenal metastases. A trend was evident toward overexpression of CCL20 in normal tissues compared with corresponding tumors (Figure 4).

Figure 4.

Representative Images of Strong CCL20 Staining in Normal Tissue Surrounding Adrenal Metastases
Magnification of samples, × 400.

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