Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer

Ohgami, Akira; Mitsudomi, Tetsuya; Sugio, Kenji; Tsuda, Tohru; Oyama, Tsunehiro; Nishida, Kazuko; Osaki, Toshihiro; Yasumoto, Kosei

doi:10.1016/s0003-4975(97)00543-2

Cited by 85 publications

(38 citation statements)

References 21 publications

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“…5,2,22 The development of relapsing disease might be attributed to local or systemic undetectable remaining viable tumor cells after resection. [5][6][7] For these reasons over the last 15 years the improvement of prognosis by postoperative chemotherapy has been attempted. Accordingly, patients completely resected for stages I and II tumors have been enrolled in adjuvant chemotherapy clinical studies.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we might hypothesize that this effect may be due to the permanence of cancer cells in circulation or hidden in lymphatic organs, which can be responsible for metastases development. 6,7 In fact, in case of anatomical surgery the residual cell load is probably lower than that occurring after minimal surgery and therefore adjuvant chemotherapy can be more effective.…”

Section: Discussionmentioning

confidence: 99%

“…standard, atypical, parenchyma-sparing or extended procedures) but all aim at the resection of NSCLC oncologically complete. Notwithstanding, long-term survival is not satisfactory and the recurrence rate is quite high [2][3][4] due to the presence of micrometastases [5][6][7] not detectable by conventional diagnostic procedures and, therefore, not eradicable by surgery. To prevent this occurrence, postoperative adjuvant systemic therapy was proposed even in the case of surgical procedures deemed radical.…”

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confidence: 99%

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Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study

Roselli

Mariotti

Ferroni

et al. 2006

Intl Journal of Cancer

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Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long-term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2-armed study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m 2 day 1) and etoposide (120 mg/m 2 days 1-3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease-free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 6 30.86 months. A significant difference in overall (p 5 0.02) and disease-free (p 5 0.0001) survival was observed between patients undergoing adjuvant chemotherapy vs. control group. Adjuvant chemotherapy significantly improved both overall (p 5 0.02) and DFS (p 5 0.003) of anatomically resected patients, but only the DFS (p 5 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long-term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected. ' 2006 Wiley-Liss, Inc.Key words: adjuvant chemotherapy; NSCLC IB; long-term survival Radical surgical resection is considered the adequate treatment in providing survival benefits for early nonsmall cell lung cancer (NSCLC), especially for those patients without lymph node involvement.1 A variety of surgical procedures exist (e.g. standard, atypical, parenchyma-sparing or extended procedures) but all aim at the resection of NSCLC oncologically complete. Notwithstanding, long-term survival is not satisfactory and the recurrence rate is quite high 2-4 due to the presence of micrometastases 5-7 not detectable by conventional diagnostic procedures and, therefore, not eradicable by surgery. To prevent this occurrence, postoperative adjuvant systemic therapy was proposed even in the case of surgical procedures deemed radical. 8,9 A recent meta-analysis of all randomized trials with accrual from January 1965 to December 1991 showed that the absolute risk of death was reduced by 3% at 2 years and 5% at 5 years for patients who were treated with postoperative cisplatin-containing regimens.10 According to these evidences some institutions, 8,9,11,12 proposed adjuvant chemotherapy even after presumed radical surgery at stage I, despite discordant results presented by another multicentr...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study

Roselli

Mariotti

Ferroni

et al. 2006

Intl Journal of Cancer

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“…It should be noted that several correlative studies between CK18 expression and prognostic value were previously established with discrepant results depending on the primary tumoral site. In this respect, an association between the induction of CK18 and a poor prognostic outcome has been established in carcinoma of the oral cavity (25) and in non-small cell lung cancer (26). Cintorino et al suggested that CK8, CK18 and CK19 expression and distribution patterns could be of predictive value as markers of disease progression as defined by the appearance of lymph node metastases in oesophageal squamous cell cancer (27).…”

Section: Discussionmentioning

confidence: 99%

Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: Relationship with Snail

Messai

Noman

Derouiche³

et al. 2010

Int J Oncol

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Abstract. Renal cell carcinoma (RCC) is the most common type of kidney cancer and recent developments in the molecular biology of RCC have identified multiple pathways associated with the development of this cancer. This study aimed at analyzing the expression pattern of cytokeratin 18 (CK18) in RCC patients and its prognostic relevance. We quantified CK18 mRNA expression and protein using real-time reverse transcription quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry, respectively, in paired tumor and non-tumor samples from 42 patients. Our data indicate that CK18 mRNA and proteins levels increased with advanced stage and grade of the disease. Using primary (RCC5) and metastatic renal cell carcinoma (RCC5 met) cell lines, we demonstrated that CK18 expression was 5-fold higher in the metastatic as compared to the primary RCC cell line and correlated with a migratory phenotype characterized by a distinct elongated morphology as revealed by Phalloidin staining. In addition, RCC5 met cells displayed an increased capacity to attach to fibronectin and collagen which was lost following CK18 knock-down. Our data also indicate that the expression of CK18 was associated with increased Snail expression which correlated positively with advanced disease in RCC patients. The present findings suggest that CK18 may play an important role in the progression of RCC and it may be used as a new predictor for RCC.

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“…8,9 This finding is not surprising, as cytokeratin 19 (CYFRA21-1) 8,10 now is used widely as a serum tumor marker for NSCLC. Ohgami et al 11 reported that patients who had cytokeratin 18 -positive cells in their bone marrow experience earlier disease recurrence compared with patients who do not. We also found increased mRNA expression of collagen family members derived from interstitial fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

Nakamura

Saji

Ogata

et al. 2003

Cancer

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BACKGROUNDThe relationship between altered gene expression and tumor progression in lung carcinoma has yet to be characterized. Gene expression in pathologic Stage IA nonsmall cell lung carcinoma specimens was analyzed using a cDNA microarray.METHODSSurgical specimens were used for the current study. The pathologic stage was IA (AJCC) in five tumors, IB in two, IIA in one, IIIA in one, and IIIB in one. Seven tumor specimens were adenocarcinomas and three were squamous cell carcinomas. Paired mRNAs from carcinoma cells and normal lung tissue specimens from the same lobe were labeled with different fluorochromes during cDNA probe synthesis in a reverse‐transcription reaction. Both synthesized, labeled cDNA probes were mixed and hybridized to the microarray. The signal intensity of each spot was measured by laser scanner and gene expression was quantified as the tumor‐to–normal fluorescence ratio (T:N ratio). The gene was overexpressed when the T:N ratio was greater than 2.0 and underexpressed when the ratio was less than 0.5.RESULTSOverall, 40 (9.4%) of the 425 genes evaluated were overexpressed, and 74 genes (17.4%) were underexpressed. In the 5 Stage IA tumor specimens, 31 (7.3%) genes were overexpressed and 76 (17.9%) were underexpressed. For 30 genes (7.1%), expression was different in Stage IA tumor specimens compared with more advanced tumor specimens.CONCLUSIONSThe cDNA microarray system showed that numerous alterations of gene expression were present in early‐stage nonsmall cell lung carcinoma specimens. Cancer 2003;97:2798–805. © 2003 American Cancer Society.DOI 10.1002/cncr.11406

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Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer

Cited by 85 publications

References 21 publications

Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study

Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study

Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: Relationship with Snail

cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

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