Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer.

Skip metastasis to mediastinal lymph nodes is a well-known phenomenon in non-small cell lung cancer (NSCLC). Little is reported in the literature about its clinical importance. It is still under discussion whether any prognostic differences exist between resected NSCLC with either skip metastases or continuous mediastinal lymph node metastases (N2). We analyzed retrospectively the data of 45 patients with a pN2-stage, who underwent resection for NSCLC. Seventeen of these patients (37.8%), showing no metastatic involvement of hilar (N1) lymph nodes, were compared to the remaining 28 patients with infiltration of hilar nodes (N1) as well as N2 nodes. Multivariate analysis showed no statistically significant difference between the skip metastasis and the continuous N2 group regarding sex, age, histology, T- or M-status. The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe (n = 12, 71%) compared to the lower lobe (n = 5, 29%). This difference was not statistically significant. In patients with a non-continuous lymph node spread, 29 out of 119 resected mediastinal lymph nodes were infiltrated (1.7 per patient, range: 1-10). Compared to 83 metastatic involved lymph nodes out of 198 resected mediastinal nodes (three per patient, range: 1-10) in patients with involvement of N1 and N2 nodes (P = 0.034, Mann-Whitney test). The 5-year survival rate of pN2 patients with skip metastasis was 41% compared to 14% in patients with involvement of N1 and N2 nodes (P = 0.019). pN2 patients with mediastinal lymph node skip metastasis have a more favorable prognosis compared to pN2 patients with continuous infiltration of the regional lymph nodes. Patients with a continuous lymph node involvement show an increased number of infiltrated mediastinal lymph nodes per patient compared to patients with a non-continuous spread. Skip metastasis is an independent prognostic factor of survival. The presence of skip metastasis seems to be a unique subgroup of pN2 disease in NSCLC.

Prenzel KL ，Mönig SP ，Sinning JM ，Baldus SE ，Gutschow CA ，Grass G ，Schneider PM ，Hölscher AH ... -  《JOURNAL OF SURGICAL ONCOLOGY》

Skip metastasis in nonsmall cell lung carcinoma: predictive markers and isolated tumor cells in N1 lymph nodes.

Skip metastasis to mediastinal lymph nodes is a prognostic factor for patients with nonsmall cell lung carcinoma (NSCLC). Little is known about the biologic behavior of tumors with noncontinuous spread to the mediastinal lymph nodes. In patients with pN2 skip metastases, micrometastases to N1 lymph nodes, which only mimic skip metastases, have not been investigated. In a retrospective study, the authors analyzed the primary tumor specimens from 45 patients with pN2 NSCLC (18 patients had squamous cell carcinomas, 23 had adenocarcinomas, and 4 had large cell carcinomas). They immunohistochemically evaluated the expression of p21, p53, MUC-1, Bcl-2, c-ErbB-2, and E-cadherin. Survival rates and biomarker expression levels were compared between patients with pN2 disease and infiltration of N1 lymph nodes (without skip metastasis [n = 28]) and patients with pN2 disease without N1 infiltration (with skip metastasis [n = 17]). To evaluate micrometastasis in the pN1 lymph nodes of 17 patients with skip metastases, lymph nodes were stained using the anticytokeratin antibody, AE1/AE3. The 5-year survival rate of patients with skip metastases was 41%, compared with 14% for patients without skip metastases (P = 0.019). In a multivariate analysis, the incidence of skip metastases did not vary significantly according to gender, age, histology, pT status, or cM status. Three skip-positive patients (17.6%) had micrometastatic tumor involvement of pN1 lymph nodes. After adding these patients to the group of patients without skip metastases, there was still a significant difference in survival between the two groups. p53, MUC-1, c-ErbB-2, and E-cadherin expression levels in primary tumor specimens were not significantly different in patients with continuous metastasis and patients with skip metastases. Patients with skip metastases expressed lower levels of p21 (P = 0.026), whereas Bcl-2 expression levels were considerably higher (P = 0.019) compared with the corresponding levels in patients without skip metastases. Patients with NSCLC and pN2 skip metastases have a more favorable prognosis than do patients with pN2 disease without skip metastases. Tumor specimens from these patients exhibit elevated expression of the antiapoptosis gene BCL2 and lower expression levels of p21 relative to patients with pN2 disease without skip metastases. Micrometastases occurred in 3 of 17 (17.6%) patients with pN2 disease and skip metastases diagnosed by routine histopathology.

Prenzel KL ，Baldus SE ，Mönig SP ，Tack D ，Sinning JM ，Gutschow CA ，Grass G ，Schneider PM ，Dienes HP ，Hölscher AH ... -  《CANCER》

Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis.

Riquet M ，Assouad J ，Bagan P ，Foucault C ，Le Pimpec Barthes F ，Dujon A ，Danel C ... -  《-》

Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors.

Okada M ，Sakamoto T ，Yuki T ，Mimura T ，Nitanda H ，Miyoshi K ，Tsubota N ... -  《JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY》

Analysis of risk factors for skip lymphatic metastasis and their prognostic value in operated N2 non-small-cell lung carcinoma.

Benoit L ，Anusca A ，Ortega-Deballon P ，Cheynel N ，Bernard A ，Favre JP ... -  《EJSO》