Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

Kronberg, Udo; López-Köstner, Francisco; Soto, G Sebastián; Zúñiga, Álvaro; Wistuba, Ignacio I.; Miranda, Vanessa da Costa; Pinto, Eliana; Viviani, Paola; Marshall, Guillermo

doi:10.1007/s10350-004-0560-9

Cited by 33 publications

(18 citation statements)

References 21 publications

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“…Relevant articles were identified through a PUBMED search using the terms "colorectal cancer," "lymph nodes," and "micrometastasis," Additional articles were identified through careful review of the referenced articles from these initially identified publications. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Thus, the reviewed studies consistently evaluate the pN0 LN from stage 1 and stage 2 CRC patients (in some studies referred to as Dukes A and B) for the presence of occult metastases. The following aspects were considered with regard to each study: i) size of study including number of stage 1 and 2 patients and percentage of rectal cancer patients; ii) method used for occult metastasis detection; iii) potential for sampling error (includes sectioning analysis, number of slides, sections, and levels of sections per LN, and number of LNs reviewed per patient); iv) quality control of original pathological diag- nosis; v) percentage of patients that were upstaged; vi) mean or median follow-up (5-year survival and recurrence data are ideal); and vii) antibodies and/or markers used for IHC or PCR.…”

Section: Search Methods and Article Selectionmentioning

confidence: 99%

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Nicastri

Doucette

Godfrey

et al. 2007

The Journal of Molecular Diagnostics

171

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The clinical significance of micrometastasis of colorectal cancer (CRC) to regional lymph nodes remains controversial. In this review, we analyze publications that have evaluated the clinical significance of occult lymph node metastasis in CRC. An extensive literature search identified 19 publications that evaluated the clinical significance of micrometastatic CRC by various methods, including immunohistochemistry (IHC; n ‫؍‬ 13) and reverse transcription-polymerase chain reaction (RT-PCR, n ‫؍‬ 6). These studies were reviewed for methodology and findings. Significant limitations in methodology were identified, including inconsistent histological definitions of micrometastatic disease, poor sampling because of an inadequate number of lymph nodes or number of sections per lymph node analyzed, lack of conformity with respect to IHC antibody or RT-PCR marker, and inadequate power because of small sample size. Micrometastatic lymph node metastasis identified by RT-PCR was consistently found to be prognostically significant, but this was not true of micrometastatic disease identified by IHC. RT-PCR analysis of lymph nodes with specific markers can help identify pN0 (pathological-negative lymph node) CRC patients at increased risk for recurrence. The identification of occult disease by IHC techniques may also ultimately prove to be associated with worse outcome, but a number of inadequately powered studies have concluded conversely.

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Section: Search Methods and Article Selectionmentioning

confidence: 99%

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Nicastri

Doucette

Godfrey

et al. 2007

The Journal of Molecular Diagnostics

171

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“…With IHC and molecular genetics methods, occult tumor cells in regional lymph nodes are detected in 25% to 50% of patients with node-negative colorectal cancer (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Because up to 25% of patients with node-negative colorectal cancer ultimately die as a result of disease relapse, occult cancer metastasis has been suspected as a potential marker for systemic spread of tumor cells (1).…”

Section: Introductionmentioning

confidence: 99%

“…Because up to 25% of patients with node-negative colorectal cancer ultimately die as a result of disease relapse, occult cancer metastasis has been suspected as a potential marker for systemic spread of tumor cells (1). However, the prognostic value of molecular tumor cell detection in patients with node-negative colorectal cancer has remained uncertain because of lack of evidence from prospective studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Yamamoto

Murata

Fukunaga

et al. 2016

Clinical Cancer Research

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Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n ¼ 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P ¼ 0.001) and 5-year overall survival (OS; P ¼ 0.016).Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer.

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“…The presence of micrometastases (MCMs) within LNs that are not detected by conventional hematoxylin and eosin (H-E) staining provides a possible explanation for this discrepancy. However, although the presence of LN MCMs in CRC patients has been investigated, no consensus has been reached regarding the prognostic significance of this finding (4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer

2008

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Purpose: A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer. Materials and Methods:The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival.Results: Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis.Conclusions: Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining.

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Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

Abstract: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.

Cited by 33 publications

References 21 publications

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer

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