Micrometastases and Survival in Stage II Colorectal Cancer

Liefers, G-J; Cleton-Jansen, A.M.; Cj, van de Velde; Hermans, Jos; Jh, van Krieken; Cj, Cornelisse; Ra, Tollenaar

doi:10.1056/nejm199807233390403

Cited by 542 publications

(348 citation statements)

References 23 publications

Supporting

Mentioning

308

Contrasting

Unclassified

Order By: Relevance

“…Despite a potential curability rate of ≥70% for patients suffering from colon cancer, the overall 5-year survival rate is just over 30% (1,2). Although many patients present with tumors that are surgically resectable, a large number of patients die from recurrent disease after apparently curative surgery.…”

Section: Discussionmentioning

confidence: 99%

Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

Schoppmeyer

Frühauf²,

Oldhafer³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

Abstract. Patients undergoing resection of hepatic metastases of colorectal cancer have a high risk of extrahepatic recurrence, most likely caused by early tumor cell dissemination or the manipulation of liver tumors during surgical resection. Using immunocytochemistry, we studied 47 patients for cytokeratin (CK)-positive (+) cells in: a) bone marrow (BM) samples to determine whether tumor cell dissemination had already occurred before surgery; and b) blood samples directly taken from the hepatic vein before and during surgery of liver metastases. In addition, normal and malignant liver tissues were evaluated for markers known to be involved in tumor progression and metastasis [urokinase plasminogen activator (uPA), Her-2/neu, epidermal growth factor receptor (EGF-R)] using sandwich enzyme immunoassays. CK + cells were detected in the BM of 26/47 patients (55%), in blood samples of 14/47 patients (30%) before surgery and 11/47 patients (23%) during surgery with a median detection rate of 1 (range, 1-14) CK + cell per 4x10 6 MNC. No CK + cells were found in 15/47 patients (32%) in any sample studied. Tumor tissue was obtained from 32/47 patients and normal liver tissue from 24/32 patients. While no differences were found for EGF-R and Her-2/neu, a 9-fold higher expression of uPA could be demonstrated in tumor tissue of 20/32 patients (63%) compared to normal liver tissue. When all obtained results were correlated with clinical outcome, neither the detection of CK + cells nor the expression pattern in the tumor tissue, or the combination of both, was predictive for extrahepatic recurrence or overall survival after a mean observation time of 43 months (range, 26-54 months). Although uPa is overexpressed in liver metastases of colorectal cancer, and dissemination of CK + cells during surgery of these metastases is a frequent event in colon cancer, these findings do not predict extrahepatic recurrence. Further characterization of single cells, especially those spread during surgery, will help to identify those patients with an increased risk of later relapse.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

Schoppmeyer

Frühauf²,

Oldhafer³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Por outro lado, outros investigadores sustentaram que a identificação de micrometástases linfonodais teria influência negativa na sobrevivência dos seus portadores 3,17,21 . De qualquer modo, observa-se que doentes com carcinoma colorretal com estádio B de Dukes representam grupo heterogêneo, onde 50% evoluem de maneira satisfatória, enquanto a outra metade destes enfermos exibe prognóstico semelhante ao dos doentes com estádio C de Dukes 22 .…”

Section: Resultsunclassified

“…Apesar do uso de diferentes procedimentos diagnósti-cos, no momento da cirurgia muitos doentes apresentam o tumor em estádio avançado e nos enfermos com lesões extirpá-veis a sobrevivência de cinco anos atinge somente cerca de 50% 2,3 .…”

Section: Introductionunclassified

See 1 more Smart Citation

Significado prognóstico das micrometástases nos linfonodos do carcinoma colorretal: detecção imunoistoquímica com anticorpos anticitoqueratina AE1/AE3

Palma¹,

Waisberg

Simões

et al. 2002

Rev. Col. Bras. Cir.

View full text Add to dashboard Cite

RESUMO: Objetivos:Identificar por imunoistoquímica eventuais micrometástases nos linfonodos regionais previamente considerados livres pelo exame histopatológico convencional e avaliar a influência do comprometimento destes linfonodos na sobrevivência dos doentes com carcinoma colorretal extirpado com intenção curativa. Método: Foram estudados 51 doentes portadores de carcinoma colorretal nos estádios A (13 casos) e B (38 casos), segundo a classificação de Dukes. Um total de 501 linfonodos previamente considerados livres pelo exame histopatológico convencional foi investigado por meio de técnica imunoistoquímica com anticorpos monoclonais anticitoqueratina AE1/AE3 para identificar células epiteliais. Cada bloco previamente fixado em formalina e embebido em parafina foi seccionado em três partes, obtendo-se de cada uma delas três cortes com espessura de 4 milimícron cada. Resultados: Em seis doentes (11,7%) no estádio B de Dukes, células neoplásicas foram identificadas em sete linfonodos do mesocolo (1,4%) previamente considerados livres de neoplasia pelo exame histopatológico convencional. Em um enfermo, a micrometástase era representada por aglomerado celular, enquanto que nos outros cinco doentes as micrometástases eram constituídas por células isoladas. A sobrevivência dos enfermos com micrometástases linfonodais foi menor do que a dos doentes com linfonodos não comprometidos, porém sem atingir diferença significativa. Conclusões: O método imunoistoquímico pode ser empregado com sucesso na detecção de células neoplásicas em linfonodos previamente considerados livres pelo exame histopatológico convencional. O acometimento dos linfonodos regionais por micrometástases não influenciou a sobrevivência dos doentes com carcinoma colorretal extirpado.Descritores: Neoplasias do colo; Prognóstico; Linfonodos; Estadiamento de neoplasia; Imunoistoquímica. 131 INTRODUÇÃOO carcinoma colorretal é uma das doenças malignas mais freqüentes no mundo ocidental e sua incidência está em elevação 1 . Apesar do uso de diferentes procedimentos diagnósti-cos, no momento da cirurgia muitos doentes apresentam o tumor em estádio avançado e nos enfermos com lesões extirpá-veis a sobrevivência de cinco anos atinge somente cerca de

show abstract

“…Although Dukes' classification remains a powerful predictor of final outcome for colorectal cancer patients (Dukes, 1932;Deans et al, 1992), the traditional clinicopathological predictors are not yet fully successful at predicting recurrence and survival risks for patients with Dukes' stage B and C cancers (Liefers et al, 1998). Our data on cathepsin H suggest that this new proteinase marker might be particularly useful in defining Dukes' B and C stage cancers and in distinguishing subsets of cancers at a given site.…”

Section: Discussionmentioning

confidence: 99%

Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas

Shuja

Cai

et al. 2000

Br J Cancer

View full text Add to dashboard Cite

SummaryOur analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in colorectal cancers compared to control mucosa (P = 0.003; n = 77). Highest specific activities and cancer/normal ratios (C/N) for activity were measured in Dukes' B and C stage carcinomas, cancers involved in local spread and invasion to lymph nodes. In contrast, cathepsin B and L activities analysed in the same paired extracts had been shown to be most frequently elevated in earlier stage carcinomas (Dukes' A and B), confirming that cathepsin H demonstrates a distinct pattern of expression during colorectal cancer progression. Although cathepsin H activities were most commonly elevated in Dukes' C cancers at all colon sites, both specific activity and C/N ratios were significantly higher for cancers of the left colon compared to other colon locations. A subset of 43 paired extracts analysed on Western blots also revealed consistent changes in cathepsin H protein forms in cancers. Normal mucosa typically showed a strong protein doublet at 31 and 29 kDa while cancers demonstrated decreased expression or total loss of the 31 kDa protein (90% of cases), equal or increased expression of the 29-kDa protein (67% of cases) and the new appearance or up-regulation of a cathepsin H band at 22 kDa (78% of cases). C/N ratios for cathepsin H enzyme activity correlated significantly with C/N ratios for the 29 kDa mature single-chain protein form (P < 0.001), with increased activity most commonly associated with elevated expression of 29-kDa cathepsin H but also with up-regulation of the 22-kDa band, suggesting a shift to more fully processed, mature active cathepsin H protein forms in cancers. Changes in cathepsin H expression were also detected by immunohistochemistry as elevated cathepsin H staining in tumour epithelial cells.

show abstract

Micrometastases and Survival in Stage II Colorectal Cancer

Abstract: Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.

Cited by 542 publications

References 23 publications

Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

Significado prognóstico das micrometástases nos linfonodos do carcinoma colorretal: detecção imunoistoquímica com anticorpos anticitoqueratina AE1/AE3

Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas

Contact Info

Product

Resources

About