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Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer.

Nordgård O, Singh G, Solberg S, Jørgensen L, Halvorsen AR, Smaaland R, Brustugun OT, Helland Å - PLoS ONE (2013)

Bottom Line: LN and PB marker status were compared to clinicopathological patient data.A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. nood@sus.no

ABSTRACT

Introduction: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).

Methods: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.

Results: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).

Conclusions: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

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Related in: MedlinePlus

Marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN), patient LNs (ptN), normal blood (nB) and patient blood (ptB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and are not directly comparable.
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pone-0062153-g003: Marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN), patient LNs (ptN), normal blood (nB) and patient blood (ptB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and are not directly comparable.

Mentions: To further validate the 5 markers in the refined panel, we determined their relative levels in tumors (including the 16 from the initial validation), regional LNs, and PB samples from 55 NSCLC patients undergoing surgical treatment (Figure 3). A total of 84 LNs from the 55 patients were examined (mean 1.5 LN/patient, range 1–3). Some of the patients’ LNs and PB samples had elevated levels compared with the normal controls. However, marker levels in LNs retrieved from patients with positive node status (pN+) according to routine histological assessment were not significantly different from the other LNs, although there were clear trends for some of the markers (data not shown). We used the highest normal level of each marker as a threshold to define pathology in LNs and PB samples, since elevated levels most likely were due to the presence of tumor cells. Based on these thresholds, we determined the number of patients positive for each tumor cell marker in LNs and PB samples (Table 3). In total, 39 (71%) of the 55 patients were positive for at least one marker in the examined LNs, whereas 26 (47%) of the patients had positive PB samples. For LNs, all five markers contributed substantially to the identification of patients with molecular evidence of LN metastases. In PB samples, KRT19 mRNA played a predominant role in identifying potential circulating tumor cells. Considerable overlap between the different markers was observed. There was no statistically significant association between LN and PB marker status.


Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer.

Nordgård O, Singh G, Solberg S, Jørgensen L, Halvorsen AR, Smaaland R, Brustugun OT, Helland Å - PLoS ONE (2013)

Marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN), patient LNs (ptN), normal blood (nB) and patient blood (ptB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and are not directly comparable.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643953&req=5

pone-0062153-g003: Marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN), patient LNs (ptN), normal blood (nB) and patient blood (ptB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and are not directly comparable.
Mentions: To further validate the 5 markers in the refined panel, we determined their relative levels in tumors (including the 16 from the initial validation), regional LNs, and PB samples from 55 NSCLC patients undergoing surgical treatment (Figure 3). A total of 84 LNs from the 55 patients were examined (mean 1.5 LN/patient, range 1–3). Some of the patients’ LNs and PB samples had elevated levels compared with the normal controls. However, marker levels in LNs retrieved from patients with positive node status (pN+) according to routine histological assessment were not significantly different from the other LNs, although there were clear trends for some of the markers (data not shown). We used the highest normal level of each marker as a threshold to define pathology in LNs and PB samples, since elevated levels most likely were due to the presence of tumor cells. Based on these thresholds, we determined the number of patients positive for each tumor cell marker in LNs and PB samples (Table 3). In total, 39 (71%) of the 55 patients were positive for at least one marker in the examined LNs, whereas 26 (47%) of the patients had positive PB samples. For LNs, all five markers contributed substantially to the identification of patients with molecular evidence of LN metastases. In PB samples, KRT19 mRNA played a predominant role in identifying potential circulating tumor cells. Considerable overlap between the different markers was observed. There was no statistically significant association between LN and PB marker status.

Bottom Line: LN and PB marker status were compared to clinicopathological patient data.A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. nood@sus.no

ABSTRACT

Introduction: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).

Methods: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.

Results: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).

Conclusions: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

Show MeSH
Related in: MedlinePlus