Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma

Sis, B.; Sarıoğlu, Sülen; Sökmen, Selman; Şakar, Mustafa; Küpelioğlu, Ali; Füzün, Mehmet

doi:10.1136/jcp.2004.018705

Cited by 56 publications

(48 citation statements)

References 29 publications

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“…The composition of tumours varies dramatically among patients and has previously been linked to differential survival in the breast (Baak et al, 1985), lung (Nakajima, 1991;Maeshima et al, 2002;das Neves Pereira et al, 2004), skin (Breuninger et al, 1997), prostate cancer (Yanagisawa et al, 2007) and CRC (Halvorsen and Seim, 1989;Shepherd et al, 1997;Sis et al, 2005;Ngan et al, 2007;Tsujino et al, 2007). Most of these studies demonstrate that a greater proportion of stroma or an exaggerated desmoplastic response is associated with poorer patient outcomes (Jass, 1986;Roncucci et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

et al. 2010

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BACKGROUND: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer. METHODS: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses. RESULTS: Tumours with PoT-low (p47%) were associated with significantly lower cancer-specific survival when compared to PoT-high (hazard ratio (HR) ¼ 2.087, 95% CI ¼ 1.088 -4.003, P ¼ 0.024). On sub-analysis, the prognostic effect remained significant in colonic tumours (HR ¼ 2.474, 95% CI ¼ 1.132 -5.408, P ¼ 0.019) and tumour, node, metastasis stage III disease (HR ¼ 3.480, 95% CI ¼ 0.325 -9.136, P ¼ 0.007). Multivariate Cox regression analysis demonstrated that PoT was an independent prognostic marker when adjusted for age, T stage, N stage and extramural vascular invasion (P ¼ 0.017). CONCLUSION: This study suggests that a low proportion of tumour cells in colorectal cancer is related to poor cancer-specific survival. A relatively quick, inexpensive and well-established method such as point counting on diagnostic tissue sections could be used to identify a subset of patients who may benefit from adjuvant therapy.

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Section: Discussionmentioning

confidence: 99%

“…In CRC, the number of stromal myofibroblasts , vimentin expression and degree of stromal desmoplasia (Halvorsen and Seim, 1989;Shepherd et al, 1997;Sis et al, 2005) have been associated with patient prognosis in the past. So far, only one study has suggested that the proportion of tumour cells in CRC may be important (Mesker et al, 2007).…”

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The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

et al. 2010

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“…1 In colorectal carcinomas, marked tumor invasion and expansion of the stroma are well-known features associated with metastasis and poor prognosis. [2][3][4] As a mouse model for colorectal adenocarcinomas, we previously constructed cis-Apc þ /D716 Smad4 þ /À compound mutant (hereafter cis-Apc/Smad4 mice) carrying a knockout allele of the Smad4 gene on the same chromatid as that of Apc. 5 Using these mice, we demonstrated that loss of SMAD4-dependent TGF-b family signaling converts intestinal adenomas to adenocarcinomas.…”

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confidence: 99%

Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas

Kitamura

Biyajima

Aoki

et al. 2009

Laboratory Investigation

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Expression of matrix metalloproteinase 7 (MMP7) is increased in the human colorectal carcinomas, and correlates with malignant progression. However, its contribution to colon cancer pathogenesis is not understood thoroughly. To investigate the roles of MMP7 in colon cancer progression, we introduced an Mmp7 knockout mutation into the cis-Apc/Smad4 mutant mouse, a model of invasive colon cancer in which SMAD4-dependent TGF-b family signaling is inactivated. We demonstrate here that lack of MMP7 reduces the number and size of tumors in the cis-Apc/Smad4 mice. On the other hand, MMP7-deficiency does not affect the depth of tumor invasion, number of stromal fibroblasts or levels of extracellular matrix components in the tumors. These results indicate that MMP7 is required for tumor formation, but not for the invasion or fibrosis of the colon cancer whose SMAD4-dependent TGF-b family signaling is blocked. Accumulating evidence suggest that most colorectal adenomas are initiated by the inactivation of APC gene, and progress into adenocarcinomas through additional genetic alterations in KRAS (for KRAS), TP53 (P53), SMAD4, TGFBR2 (TGF-b type-II receptor), etc. 1 In colorectal carcinomas, marked tumor invasion and expansion of the stroma are well-known features associated with metastasis and poor prognosis. [2][3][4] As a mouse model for colorectal adenocarcinomas, we previously constructed cis-Apc þ /D716 Smad4 þ /À compound mutant (hereafter cis-Apc/Smad4 mice) carrying a knockout allele of the Smad4 gene on the same chromatid as that of Apc. 5 Using these mice, we demonstrated that loss of SMAD4-dependent TGF-b family signaling converts intestinal adenomas to adenocarcinomas. Namely, the cis-Apc/ Smad4 mice develop tumors that show marked invasion and stromal expansion, although the simple Apc mutant (Apc D716 ) mice form only benign adenomas. 5,6 To examine the mechanisms underlying such malignant changes in the cis-Apc/Smad4 tumors, we recently performed DNA microarray analyses and found that the adenocarcinomas expressed much higher levels of CC-chemokine ligand 9 (CCL9) than the Apc D716 adenomas. Further studies revealed that CCL9 released from the cis-Apc/Smad4 tumor epithelia recruits immature myeloid cells (iMCs) that carry its CC-chemokine receptor (CCR1) and express matrix metalloproteinase (MMP) 2 and 9 to help tumor invasion. 7 Although it is the tumor stromal cells that produce most MMPs whose levels are increased in the colon cancer (eg MMP2 and MMP9), the tumor epithelial cells can express another MMP, MMP7. 8 Interestingly, our microarray data 7 showed increased expression of MMP7 in the cis-Apc/Smad4 adenocarcinomas compared with the Apc D716 adenomas. In human colorectal cancer, it has been reported that the level of MMP7 correlates with advanced Dukes stages, poor outcome, invasion and metastasis to the liver. 9-11 Several studies have shown that overexpression of MMP7 increases the invasive ability and metastasis to the liver in some colon cancer cell lines, 9,12,13 although another study suggests ...

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“…Reproducibility and reliability analyses have previously showed that the measurement of SAP by computer assisted image analysis is a highly reliable method (the coefficient of intraclass correlation = 0.98) (Sis et al 2005). (Francis 1990).…”

Section: Image Analysismentioning

confidence: 99%

“…Images were processed with Mediscope Image Analysis Software (Mediscope, Dokuz Eylul University, Clinical Engineering Department, Izmir, Turkey) (Kavukcu et al 2003;Demiral et al 2004;Sarioglu et al 2004;Sis et al 2005). For each case, after detection of the most severely scarred areas by eye, 5 high power fields were selected for digital acquisition (total area: 79,390 μ m 2 ).…”

Section: Image Analysismentioning

confidence: 99%

Glutamine Administration Enhances the Healing of Lung Parenchymal Injuries and Reduces Air Leakage in Rats

Şanli

Önen

Sarıoğlu

et al. 2006

Tohoku J. Exp. Med.

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Beneficial effects of glutamine on wound healing are well known. Parenchymal injuries in the lung cause air leakage that resolves with wound healing. We aimed to determine the effect of glutamine on the healing of lung injuries. Wistar albino female rats were randomized in three groups. One group (control, n = 7) received intraperitoneal injection of 0.9% sodium chloride (1.5 ml /day), while other group (GLN, n = 7) received glutamine (1.5 g/kg/day), beginning two days prior to the operation for total four days. After thoracotomy, a lung parenchymal lesion was made with a scalpel in the right upper lobe. Only thoracotomy was performed to sham group (n = 4). Air leakage was observed in the isolated lungs of control group, but not GLN and sham groups, at 5 cm H 2 O of positive airway pressure ( p < 0.001). The threshold of positive airway pressure for air leakage was 4.85 ± 0.37 and 19.42 ± 4.54 cm H 2 O for control and GLN groups, respectively ( p < 0.001). For measurement of collagen content in the healing parenchyma, digital images were processed to calculate the stained area percentage (SAP). SAP for immature collagen, a marker for wound healing, was 0.36 ± 0.18% and 1.48 ± 0.83% ( p = 0.02) in control and GLN groups, respectively, but no significant difference was noted in SAP for mature collagen. The grade of inflammation was not significantly different between control and GLN groups. We conclude that glutamine enhances lung parenchymal healing by increasing immature collagen secretion.glutamine; collagen; air leakage; lung

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Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma

Cited by 56 publications

References 29 publications

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas

Glutamine Administration Enhances the Healing of Lung Parenchymal Injuries and Reduces Air Leakage in Rats

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