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Veli-Matti Kosma

Publications and source records attributed to Veli-Matti Kosma.

At least 19 recordsLinked to original sources
PubMed2007

No observed local immunological response at cell level after five years of oats in adult coeliac disease.

OBJECTIVE: Our earlier 5-year follow-up study produced the first evidence to show the long-term safety of oats as part of a coeliac diet. The objective of the present study was to clarify its applicability by analysing local cellular immunological responses after 5 years' consumption of oats by adult coeliac patients. MATERIAL AND METHODS: Forty-two coeliac patients took part in an earlier oats intervention study for 6-12 months. Twenty-two of these patients originally consumed oats as part of their gluten-free diet. During the 5-year follow-up 10 patients had felt uncertain about the safety of long-term consumption of oats and gave up this part of their diet. Finally, 12 of the 22 patients consumed oats for the whole 5-year period. The control group consisted of the remaining 20 coeliac patients using a strict, conventional, gluten-free diet without oats. Intraepithelial CD3, alphabetaTCR (alphabetaIEL) and gammadeltaTCR (gammadeltaIEL) T cells were counted after specific staining of small intestinal biopsy specimens. RESULTS: There were no differences in the densities of CD3, alphabetaIEL and gammadeltaIEL T cells between the oat and the control groups. CONCLUSIONS: Long-term use of oats included in the gluten-free diets of patients with coeliac disease does not stimulate an immunological response locally in the mucosa of the small intestine.

Adult↗
PubMed2006

Prognostic significance of iNOS in epithelial ovarian cancer.

OBJECTIVE: To study the association of inducible nitric oxide synthase (iNOS) expression with clinicopathological factors and prognosis in epithelial ovarian cancer. METHODS: The study included 301 patients with primary epithelial ovarian cancer. iNOS expression was evaluated by immunohistochemistry using a mouse monoclonal antibody. RESULTS: iNOS positivity was observed as granular deposits in the cancer cell cytoplasm. The mean percentage of iNOS-positive cells was 50% in primary tumors (n=301), and 62% in metastatic lesions (n=43). iNOS expression correlated significantly with histological subtype of the tumor, as high (> 70%) iNOS expression was observed in mucinous tumors (p=0.009). Poorly differentiated tumors showed a tendency to low (< or = 70%) iNOS expression but without statistical significance. Low iNOS expression associated also significantly with large primary residual tumor (p=0.007) and tumor recurrence (p=0.04). The 10-year prognosis of the patients with high iNOS expression was better in disease-related survival (DRS) (p=0.009). However, in multivariate analysis only FIGO stage, primary residual tumor, and grade of the tumor were independent prognostic factors for DRS, but not the iNOS expression. CONCLUSIONS: A major proportion of human epithelial ovarian cancers expressed iNOS. The positive expression was an indicator of better disease-related survival. However, iNOS positivity could not overcome the importance of clinicopathological factors in prediction of prognosis.

Adolescent↗
PubMed2006

CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population.

We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1-9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07-6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30-19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03-2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11-5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.

Adult↗
PubMed2006

Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian cancer and its relation to beta-catenin expression.

We investigated the expression and prognostic significance of matrix metalloproteinase (MMP) -7, its relation to beta-catenin expression and clinicopathological factors in epithelial ovarian cancer. The expression of MMP-7 was analyzed immunohistochemically in a series of 284 primary epithelial ovarian cancers, their 36 metastases and 8 normal ovaries. In cancers with endometrioid histology, a high percentage area of MMP-7 expression and an intense MMP-7 signal was significantly associated with nuclear positivity of beta-catenin in cancer cells (p = 0.003, chi2 = 8.853 and p = 0.030, chi2 = 4.713, respectively). In all tumors and nonendometrioid subgroup, a low percentage area of MMP-7 positive tumor cells was significantly correlated with a high histological grade of the tumor (p = 0.003 and 0.005, respectively), in all tumors also with advanced stage of the tumor (p = 0.002) and large primary residual tumor (p = 0.005). A 10-year disease-related survival (DRS) was significantly better when the percentage area of MMP-7 expression in cancer cells was high, when compared to low (p = 0.0008). A high percentage area of intense MMP-7 signal in cancer cells predicted a significantly more favorable DRS and recurrence-free survival (RFS) (p = 0.0003 and 0.0052, respectively). In multivariate analysis, a high percentage area of intense MMP-7 signal in tumor cells was an independent prognostic factor, predicting favorable DRS and RFS. The present study showed that intense MMP-7 signal in tumor cells is an independent prognostic factor predicting better survival in epithelial ovarian cancer.

Adolescent↗
PubMed2006

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas.

Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation-dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p = 0.035) and death due to ovarian cancer (p = 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p = 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial-mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties.

Adult↗
PubMed2006

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma.

BACKGROUND: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. AIMS: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. METHODS: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. RESULTS: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. CONCLUSIONS: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.

Adolescent↗
PubMed2006

A highly reproducible xenograft model for human ovarian carcinoma and application of MRI and ultrasound in longitudinal follow-up.

OBJECTIVE: Typically, human ovarian cancer is widely disseminated at the time of diagnosis and shows extremely poor prognosis. Experimental animal models that mimic human ovarian cancer are often incomplete when compared to the full spectrum of the human disease with regard to its histological hallmarks such as the spread of carcinoma, its ability to seed the peritoneal cavity and formation of ascites. We have established and characterized a new animal model for human ovarian cancer in nude mouse. METHODS: A new cell line SKOV-3m was injected intraperitoneally in nude mice. Mice were divided in two groups A and B, which received 1 x 10(7) and 2 x 10(7) cells, respectively. Histology, immunohistochemistry, magnetic resonance imaging and ultrasound were used to analyze tumors. RESULTS: All mice had tumors within 18 days and histologically they resembled poorly differentiated human cystadenocarcinomas with bloody ascites. Mean survival of the mice was 42+/-14 and 21+/-2 days in groups A and B, respectively. Magnetic resonance imaging and ultrasound were used to confirm the presence of tumors and to monitor their growth without sacrificing the animals. CONCLUSION: This new xenograft model accompanied by noninvasive imaging is highly reproducible and likely to be very useful in testing new treatment strategies for ovarian cancer.

Animals↗
PubMed2006

Refinement of the 22q12-q13 breast cancer--associated region: evidence of TMPRSS6 as a candidate gene in an eastern Finnish population.

Although many risk factors for breast cancer are known, most of the genetic background and molecular mechanisms still remain to be elucidated. We have previously published an autosome-wide microsatellite scan for breast cancer association and here we report a follow-up study for one of the detected regions. Ten single nucleotide polymorphisms (SNP) were genotyped in an Eastern Finnish population sample of 497 breast cancer cases and 458 controls to refine the 550-kb region on 22q12-q13 and identify the breast cancer-associated gene(s) in this region. We also studied 22q12-q13 for allelic imbalance for the detection of a possible tumor suppressor gene and to see whether the breast cancer association and allelic imbalance in this region could be connected. A SNP (rs733655) in matriptase-2 gene (TMPRSS6) was detected to associate with breast cancer risk. The genotype frequencies of rs733655 differed significantly between cases and controls in the entire sample and in the geographically and genetically more homogeneous subsample with P = 0.044 and P = 0.0003, respectively. The heterozygous genotype TC was observed to be the risk genotype in both samples (odds ratios, 1.39; 95% confidence intervals, 1.06-1.83 and odds ratios, 2.11; 95% confidence intervals, 1.46-3.05). An associated two-marker haplotype involving SNP rs733655 (empirical P = 0.041) provides further evidence for breast cancer risk factor locating on 22q12-q13, possibly being TMPRSS6. Our results suggest that matriptase-2 gene is associated with breast cancer risk in the Eastern Finnish population.

Allelic Imbalance↗
PubMed2006

Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer. Relation to clinicopathological factors, beta-catenin and prognosis.

Matrix metalloproteinases (MMPs) have been shown to have a significant role in determining cancer cell behaviour. The present study was undertaken to analyze the expression and prognostic value of MMP-7 and MMP-9 in non-small cell lung cancer (NSCLC). The relationship of MMP-7 with beta-catenin was also evaluated. The study consists of 212 patients with resected NSCLC. Tumour samples were stained immunohistochemically, and the expression of MMP-7 and MMP-9 was evaluated in both tumour cells and peritumoural stromal tissue. The results were compared to clinicopathological factors of the patients. A high staining of MMP-7 and MMP-9 in tumour cells was noted in 62 (30%) and 113 (57%) cases, respectively. Expression of MMP-7 was noted more often in adenocarcinomas than in other histological types (p=0.022). High cancer cell associated MMP-7 was related to lower T-factor (p=0.037), better tumour differentiation (p=0.005) and normal beta-catenin expression in tumour cells (p=0.001). A high MMP-9 expression in tumour cells was related to poor tumour differentiation (p=0.016). The stromal signal for MMP-9 was observed in 58 (32%) cases and was linked with higher tumour grade (p=0.031). In survival analyses the significant predictors of survival were histological type of tumour and tumour stage (p=0.0009 and 0.0012, respectively). MMP-7 or MMP-9 signals were not related to patient's outcome. The results show that high MMP-9 expression indicates aggressive, and high MMP-7 less aggressive tumour behaviour in NSCLC. However, MMP-7 and MMP-9 expressions had no prognostic value in NSCLC.

Adenocarcinoma↗
PubMed2006

Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease.

OBJECTIVE: Coeliac disease (CD) susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201. This HLA-associated risk has been estimated to account for 29-40% of the genetic component of CD. Conflicting data have been published on the gene dose effect of these HLA alleles on the risk and severity of CD. In this study the aim was to investigate the association between the number of HLA risk alleles and the severity of CD. MATERIAL AND METHODS: Fifty-four Finnish CD families, including 144 CD patients mainly diagnosed in adulthood (94.4%), were enrolled in the study. The association between the number of DQA1*0501 and DQB1*0201 alleles and villous atrophy, symptoms and laboratory parameters at the time of diagnosis, and the association with villous atrophy after one year of treatment on a gluten-free diet were studied. RESULTS: The homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy (p=0.011), younger age (p=0.036), more severe diarrhoea (p=0.048) and a lower level of blood haemoglobin at the time of diagnosis (p=0.010). Furthermore, the homozygosity for the DQB1*0201 allele was associated with a slower recovery of villous atrophy after a gluten-free diet (p=0.041). In contrast, the DQA1*0501 allele did not have a significant association with the severity of CD. CONCLUSIONS: Our results demonstrate a gene dose effect of the DQB1*0201 allele on the clinical heterogeneity of CD and on the rate of recovery from villous atrophy in patients on a gluten-free diet.

Adult↗
PubMed2006

HLA genotyping is useful in the evaluation of the risk for coeliac disease in the 1st-degree relatives of patients with coeliac disease.

OBJECTIVE: Coeliac disease (CD) is a common disease with a strong heredity. About 10-20% of 1st-degree relatives of probands develop CD. Relatives should be screened for CD, because if not treated, CD exposes patients to numerous complications. The heterogeneity of symptoms and the lifetime-spanning risk of CD render the timing of CD antibody and/or gastroscopy screenings difficult. As CD susceptibility has been shown to be strongly associated with the HLA alleles DQA1*0501 and DQB1*0201 (together encoding the DQ2 heterodimer) and DRB1*04 (associated with the DQ8 heterodimer), our aim was to investigate whether HLA genotyping might be useful in the identification of 1st-degree relatives of CD patients who do not need further screening for CD. MATERIAL AND METHODS: The study comprised 54 Finnish CD families including 54 CD probands and 382 living 1st-degree relatives. All subjects who were willing to participate were screened for CD (duodenal and skin biopsies; endomysial, reticulin and gliadin antibodies). The DQA1*0501, DQB1*0201 and DRB1*04 allele frequencies of CD patients and the 1st-degree relatives were determined. RESULTS: Altogether 17.6% (5.9% of the parents, 15.7% of the siblings, 25.8% of the offspring) of the investigated 1st-degree relatives (n = 245) did not carry any of the alleles studied. All of the CD patients (n = 136) with the exception of one (0.7%) carried at least one of the alleles investigated. CONCLUSIONS: By using the HLA genotyping a considerable proportion of 1st-degree relatives of CD probands could be excluded from further screening for CD.

Adolescent↗
PubMed2005

XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish case-control study.

INTRODUCTION: It has been suggested that individuals with reduced DNA repair capacities might have increased susceptibility to environmentally induced cancer. In this study, we evaluated if polymorphisms in DNA repair genes XRCC1 (Arg280His, Arg399Gln) and XPD (Lys751Gln) modify individual breast cancer risk, with emphasis on tobacco smoking. METHODS: The study population consisted of 483 incident breast cancer cases and 482 population controls of Finnish Caucasian origin. The genotypes were determined by PCR-RFLP-based methods. Odds ratio (OR) and confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: No statistically significant overall effect in the breast cancer risk was seen for any of the studied polymorphisms. However, a significant increase in breast cancer risk was seen among ever smoking women if they carried at least one XRCC1-399 Gln allele (OR 2.33, 95% CI 1.30-4.19, pint 0.025) or XPD-751 Gln/Gln genotype (OR 2.52, 95% CI 1.27-5.03, pint 0.011) compared to smoking women not carrying these genotypes. The risks were found to be confined to women smoking at least five pack-years; the respective ORs were 4.14 (95% CI 1.66-10.3) and 4.41 (95% CI 1.62-12.0). Moreover, a significant trend of increasing risk with increasing number of the putative at-risk genotypes (p for trend 0.042) was seen. Women with at least two at-risk genotypes had an OR of 1.54 (95% CI 1.00-2.41) compared to women with no at-risk genotypes. Even higher estimates were seen for ever actively smoking women with at least two at-risk genotypes. CONCLUSION: Our results do not indicate a major role for XRCC1 and XPD polymorphisms in breast cancer susceptibility, but suggest that they may modify the risk especially among smoking women.

Adult↗
PubMed2005

NAT2 slow acetylator genotype as an important modifier of breast cancer risk.

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case-control study, we developed a new method based on fluorogenic allele-specific probes for analyzing the C282T and T341C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity-associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01-1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29-5.24). When stratified by smoking habits, women who had smoked <5 pack-years and carried a NAT2 slow acetylator genotype were at a 2.6-fold (OR, 2.55; 95% CI, 1.01-6.48) risk of breast cancer. Moreover, women with the NAT2 slow acetylator genotype and low body mass index (BMI) (<25.4 kg/m2) were at somewhat increased risk of this malignancy (OR, 1.60; 95% CI, 1.07-2.39). Our results therefore suggest that NAT2 slow acetylator genotype may be an important modifier of environmentally induced breast cancer risk in Finnish women.

Adult↗
PubMed2005

Versican in nonsmall cell lung cancer: relation to hyaluronan, clinicopathologic factors, and prognosis.

The aim of the study was to investigate the expression and prognostic role of versican in 212 patients with resected nonsmall cell lung cancer. Tumor samples were stained immunohistochemically, and the versican staining was evaluated both in tumor stroma and cancer cells. The staining results were compared to the clinical data of the patients, the tumor cell proliferation, and the expression of hyaluronan. In the whole material, low and high area percentages of stromal versican staining were observed in 135 and 77 carcinomas, respectively. Tumor cell-associated staining signal for versican was observed in 33 cases. In the whole material, the significant relationship between high stromal staining of versican and that of hyaluronan was noticed (P = .001). The expression of stromal versican was related to tumor type (P = .008) and high stromal staining was inversely correlated with poor tumor differentiation (P = .045), but not with tumor cell proliferation. Among adenocarcinomas, the high stromal staining of versican was associated with tumor recurrence (P = .024), higher tumor stage (P = .022), and lymph node metastases (P = .042). Versican expression was not related to patient outcome in the whole material, but among adenocarcinomas, the high stromal staining was related to poor disease-free survival (P = .0056). However, in Cox multivariate analysis with tumor stage, versican expression did not retain its prognostic significance. The results indicate that increased stromal versican is related to higher tumor recurrence rate and more advanced disease. Despite the important role of versican in nonsmall cell lung cancer, traditional clinicopathologic factors remained most significant in the current study.

Adult↗
PubMed2005

Sulfotransferase 1A1 genotype as a potential modifier of breast cancer risk among premenopausal women.

SULT1A1 is involved in biotransformation of many endogenous and exogenous substrates, such as drugs, hormones and tobacco smoke carcinogens. A polymorphism in the sulfotransferase 1A1 gene (SULT1A1) results in an amino acid change from Arg to His at codon 213. The His allele (SULT1A1*2) has been shown to encode a protein with much lower catalytic activity than the protein encoded by the Arg allele (SULT1A1*1). We examined whether this polymorphism modified breast cancer risk in a Finnish-Caucasian study population consisting of 483 breast cancer patients and 482 healthy population controls. No significant genotype effects were seen in the overall breast cancer risk. However, a decreased risk of breast cancer was found among premenopausal women with at least three pregnancies and at least one SULT1A1*2 allele (odds ratio = 0.23, 95% confidence interval = 0.09-0.63) compared to women with two SULT1A1*1 alleles. Our results suggest that the SULT1A1 genotype is not an important risk factor for breast cancer in general, but may modify the risk among premenopausaul women with high parity.

Adolescent↗
PubMed2005

An autosome-wide scan for linkage disequilibrium-based association in sporadic breast cancer cases in eastern Finland: three candidate regions found.

Breast cancer is the most common of cancers among women in industrialized countries. Many of breast cancer risk factors are known, but the majority of the genetic background is still unknown. Linkage disequilibrium-based association is a powerful tool for mapping disease genes and is suitable for mapping complex traits in founder populations. We report the results of a two-stage, autosome-wide scan for LD with breast cancer. Our aim was to identify genetic risk factors for sporadic breast cancer in an eastern Finnish population. Our case-control set is from the province of northern Savo in the late-settlement area of eastern Finland. This population is relatively young and genetically homogeneous. We used 435 autosomal microsatellite markers spaced by an average of 10 cM in a set of 49 breast cancer cases and 50 controls. In the first-stage scan, we found 21 markers in LD with breast cancer (Ps = 0.003-0.046, Fisher's exact test). In the second-stage scan with markers flanking 21 positive loci, four significant markers were found (Ps = 0.013-0.046, Fisher's exact test). Haplotype analysis using global score method with two, three, or four markers also revealed four positive marker combinations (simulated P for global score = 0.003-0.021). Our results suggest breast cancer-associated regions on 3p26, 11q23, and 22q13.1 in an eastern Finnish population.

Adult↗
PubMed2004

Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis.

PURPOSE: In the present study, we investigated the expression and prognostic value of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer as well as their relation to transcription factor activator protein (AP)-2 and HER2 oncogene. The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer. EXPERIMENTAL DESIGN: MMP-2 and MMP-9 expressions were analyzed immunohistochemically in a large prospective series of 421 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital (Kuopio, Finland). The relation of MMP-2 and MMP-9 expressions to AP-2, HER2, clinicopathological data, and survival was investigated. RESULTS: Both MMP-2 and MMP-9 were expressed in the cytoplasm of malignant and stromal cells. High expression of MMPs in carcinoma cells was related to small tumors (T1, stage I), whereas positive stromal expression of MMPs was associated with aggressive factors. High expression of MMP-2 and MMP-9 in carcinoma cells, but not in stromal cells, was related to high AP-2 expression. Positive stromal MMP-2 expression was associated with HER2 overexpression in the whole patient group and in the node-negative patient subgroup. Positive stromal MMP-9 expression was related to HER2 overexpression in estrogen receptor (ER)-positive disease. In the univariate survival analysis, positive stromal MMP-9 predicted shorter recurrence-free survival (RFS; P=0.0389) and breast cancer-related survival (BCRS; P=0.0081) in ER+ disease, especially in the subgroup of ER+ tumors of < or =2 cm in diameter (T1; P=0.0031 for RFS, and P=0.0089 for BCRS). High MMP-9 expression in cancer cells predicted longer RFS (P=0.0351) in the whole patient group. In the multivariate analysis of the whole patient group, the independent predictors of shorter RFS were reduced MMP-9 expression in carcinoma cells (P=0.0248), HER2 overexpression (P=0.0001), and advanced-stage disease (P=0.0002). Shorter BCRS was predicted by advanced-stage disease (P <0.0001). CONCLUSIONS: Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2. Positive stromal MMP-9 expression predicts poor survival in the hormone-responsive small tumors, whereas MMP-9 expression in carcinoma cells favors survival. Evaluation of MMP-9 expression seems to add valuable information on breast cancer prognosis.

Adult↗