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Y Collan

Publications and source records attributed to Y Collan.

At least 19 recordsLinked to original sources
PubMed2007

DNA image cytometry is a useful adjunct tool in the prediction of disease outcome in patients with stage II and stage III colorectal cancer.

BACKGROUND: We assessed the prognostic value of the nuclear DNA content measured in the primary tumours of 123 patients with stage II or stage III colorectal cancer (CRC). METHODS: Isolated nuclei from paraffin sections were stained with the Feulgen reaction, and DNA was measured using a computer-assisted image analysis cytometry system. We applied 4 different approaches in the analysis of DNA histograms: the ABCDE approach, histogram range, peak evaluation and DNA cut-off values. RESULTS: Using the histogram range, the narrow range was rare (3.7%) in patients who died of disease (n = 28) as compared with 16.4% among those alive (n = 74; p = 0.017). Modal peak evaluation was a significant predictor of disease-free survival (DFS; Kaplan-Meier log-rank p = 0.0235). In the range evaluation, the 1st set (low-start gates) was a significant predictor of DFS (log-rank p = 0.0121), where disease recurrence was closely associated with the widest range (1.8->10c; c = haploid DNA content) gates. Recurrence-free survival was 3 times better in narrow-gate histograms than wide-range histograms (p < 0.03). The 1st set also proved to be a significant predictor of disease-specific survival (DSS; log-rank p = 0.0045), which was markedly better (77.8-90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into 2 categories (with 6.0c as cut-off), was a powerful predictor of both DSS (log-rank p = 0.0092) and 5-year DFS (p = 0.0106) in the whole series, and separately in stage III (but not stage II) disease, with p = 0.0131 and p = 0.0201, respectively. CONCLUSION: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy.

Aged↗
PubMed2006

Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

Prognosticators evaluating survival in breast cancer vary in significance in respect to lymph node status. Studies have shown e.g. that HER2/neu immunohistochemistry or HER2/neu gene amplification analysis do perform well as prognosticators in lymph node positive (LN +) patients but are less valuable in lymph node negative (LN -) patients. We collected data from different studies and tried to evaluate the relative significance of different prognosticators in LN+/LN- patient groups. In LN+ patients HER2/neu and E-cadherin immunohistochemistry were the statistically most significant prognosticators followed by proliferation associated features (mitotic counts by SMI (standardised mitotic index) or MAI (mitotic activity index), or S-phase fraction). Bcl-2 immunohistochemistry was also significant but p53 and cystatin A had no significance as prognosticators. In LN- patients proliferation associated prognosticators (SMI, MAI, Ki-67 index, PCNA immunohistochemistry, S-phase fraction) are especially valuable and also Cathepsin D, cystatin A, and p53 are significant, but HER2/neu or bcl-2, or E-cadherin less significant or without significance. We find that in studies evaluating single prognosticators one should distinguish between prognosticators suitable for LN+ and LN- patients. This will allow the choice of best prognosticators in evaluating the prospects of the patient. The distinction between LN+ and LN- patients in this respect may also be of special value in therapeutic decisions.

Journal Article↗
PubMed2006

Prognostic factors in prostate cancer.

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking.

Journal Article↗
PubMed2006

Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index.

AIMS: Counting mitotic figures is considered to be a reliable prognosticator, but evaluation of Ki67 immunohistochemistry has become more popular in evaluating proliferation. Our previous studies suggested an occasional discrepancy between mitotic figures and Ki67 fraction. The aim of this study was to investigate this more closely and also to study the associations between bcl-2 and p53 expression and proliferation. METHODS AND RESULTS: Two hundred and sixty-five infiltrating breast carcinomas were immunostained for Ki67, p53 and bcl-2. The standardized mitotic index (SMI) was determined. Four proliferation groups were based on Ki67 positivity fraction and SMI at optimal cut-off points. Cox's multivariate model was used to test the power of the prognosticators. SMI and nodal status were the most powerful individual prognosticators. Ki67 was an independent prognosticator if nodal status, tumour size, age and histological grade were included in the analysis but not if analysed with SMI. The group with low SMI and low Ki67 fraction had the best prognosis. Groups with high SMI had the poorest prognosis. The group with low SMI and high Ki67 fraction had a favourable prognosis. Bcl-2 negativity and p53 positivity correlated with proliferation. CONCLUSIONS: We have found a 'wrong positive' Ki67 group with favourable prognosis. SMI cannot be replaced by Ki67 because of the danger of misclassification of some patients.

Adult↗
PubMed2006

Comparison of CD44 expression in primary tumours and metastases of colorectal cancer.

A better understanding on the development of a metastatic phenotype in colorectal cancer (CRC) is essential to help identify patients at high risk for metastasis. Therefore, we have studied the role of the CD44 family of trans-membrane glycoprotein in the process of CRC metastasis, by examining the expression of CD44s and CD44v6 in primary tumours and their metastatic lesions in 46 patients using immunohistochemistry. The expression of both CD44s and CD44v6 was significantly higher (moderate/strong) in primary tumours as compared to their metastases (p=0.008, p=0.0001, respectively). CD44s expression in metastases increased with the degree of the histological grade (p=0.009) and invasiveness of the primary tumour (p=0.002). Disease-free survival (DFS) was shorter in patients who had metastases with a strong/moderate expression of CD44s as compared to those with negative/weak expression (8.3 months vs 16.9 months p=0.221, respectively). Our finding that CD44s expression in metastatic lesions may reflect the aggressiveness of the primary tumour from which it has originated implicates an important link between the two lesions. CD44 expression may also provide valuable biological information as suggested by the observation that up-regulated CD44s expression in metastases is associated with a shorter DFS.

Colorectal Neoplasms↗
PubMed2005

E-cadherin, CD44s and CD44v6 correlate with tumour differentiation in colorectal cancer.

Cell adhesion molecules (CAMs) are cell surface glycoproteins that are important in cell-cell and cell-matrix interactions and play an important role in cell growth and differentiation. We examined immunohistochemically CD44s, CD44v6 and E-cadherin expression in 86 formalin-fixed, paraffin-embedded primary tumours and 5 metastases. Lower levels of CD44s, CD44v6 and membranous E-cadherin expression were significantly associated with higher tumour grade (p=0.022, p=0.016 and p= 0.041, respectively). Moreover, CD44v6 and membranous E-cadherin expression were correlated with the depth of primary tumour invasion (p=0.030 and p=0.020, respectively), and increased expression of CD44v6 and decreased membranous E-cadherin expression were associated with increased primary tumour invasion. The results suggest that these CAMs are associated with tumour differentiation and invasion in locally advanced and metastatic colorectal carcinoma.

Adult↗
PubMed2004

Response to chemotherapy (irinotecan plus 5-fluorouracil) in colorectal carcinoma can be predicted by tumour DNA content.

OBJECTIVE: The aim of this study was to identify markers that might predict response to chemotherapy. Postoperative chemotherapy improves the outcome in stage III colon cancer and is widely accepted as a standard therapy, but there are currently no reliable predictors to identify and select patients that will benefit. METHODS: Using DNA image cytometry, the DNA content was determined from the isolated nuclei of 56 primary colorectal carcinomas of patients who received chemotherapy (either irinotecan or irinotecan plus 5-fluorouracil and folinic acid) for advanced disease. Response to chemotherapy could be reliably evaluated in 53 patients. RESULTS: The modal DNA content (ploidy status) of the tumour correlated with the observed response to chemotherapy (p = 0.01). An objective response was observed in 56% of patients whose tumour histograms displayed tetraploid, peri-tetraploid or multiploid patterns of peaks, compared with 19% in patients with diploid, peri-diploid or aneuploid peaks. Notably, 86% (6/7) of patients whose tumours displayed a multiploid peak pattern showed an objective response and 1 patient had stable disease. CONCLUSIONS: This study suggests that modal DNA content can be used to predict a patient's response to chemotherapy in advanced colorectal carcinoma. This may help in identifying patients who will benefit most from therapy for advanced colorectal cancer.

Adult↗
PubMed2003

Apoptotic index and bcl-2 expression as prognostic factors in colorectal carcinoma.

OBJECTIVES: To examine programmed cell death in 57 colorectal carcinomas (49 primary tumours and 8 metastases) and determine the prognostic significance of apoptosis in colorectal cancer. METHODS: Apoptotic index (AI) was ascertained by counting apoptotic bodies, using terminal deoxynucleotidyl transferase mediated digoxigenin nick end labelling (Tunel assay) and the expression of bcl-2 was examined immunohistochemically. Statistical analysis was used to test the value of clinical variables, histopathological data, AI and bcl-2 expression in predicting the clinical outcome of these patients and the survival function was calculated using the Kaplan-Meier method. RESULTS: AI was found to have a significant independent effect on survival (p = 0.0006), with lower values of AI conveying better survival. CONCLUSION: In summary, these findings reveal that AI is a useful prognostic factor in colorectal carcinoma.

Adult↗
PubMed2002

Morphometrical malignancy grading is a valuable prognostic factor in invasive ductal breast cancer.

The aim of the present study is to augment the prognostic power of breast cancer grading by elaboration of quantitative histopathological methods. We focus on the recently introduced morphometrical grading system in which the three grading sub-features of the WHO grading system are evaluated with the help of computerised nuclear morphometry, and quantitative methods for assessing mitotic activity and tubular differentiation. The prognostic value of the morphometrical grading system is now confirmed in a material of 159 cases of invasive ductal breast cancer. In the current material the morphometrical grading system very efficiently predicted the prognosis of breast cancer by dividing the patients into favourable (grade I), intermediate (grade II), and unfavourable (grade III) outcome (P<0.0001). The morphometrical grading system was especially efficient in identifying patients with the most unfavourable outcome. In our material the morphometrical grade III was associated with a 5.4-fold risk of breast cancer death. In light of the present results, the morphometrical grading can be applied to clinical use as an aid in treatment decisions of patients with invasive ductal breast cancer.

Adult↗
PubMed2002

Unbiased morphological measurements show no neuronal loss in the substantia nigra in Alzheimer's disease.

This is the first study to use the unbiased stereological method, the disector, to estimate the total number of pigmented neurons in the pars compacta of the substantia nigra (SNpc) in Alzheimer's disease (AD) patients as compared to healthy controls. The right half of the SNpc of 11 AD patients and 24 controls was studied. We also used single sections to determine the neuronal number and area in different subregions of the SNpc. The results showed that there was no significant difference in the total number of pigmented neurons in the SNpc (154,415+/-13,593 for AD and 160,163+/-8027 for controls) or in the volume of the SNpc between the patients with AD and controls. Studies on single sections revealed that even subregionally there was no significant difference in the neuronal number or area in the SNpc between AD patients and controls.

Adolescent↗
PubMed2002

Prognostication of invasive ductal breast cancer by quantification of E-cadherin immunostaining: the methodology and clinical relevance.

AIMS: We tried to improve the evaluation of E-cadherin immunostaining in paraffin sections, to distinguish the less aggressive variants of ductal infiltrating breast cancer from other variants. METHODS AND RESULTS: The method graded the membrane staining and estimated the fraction of area of cancer tissue stained at the respective staining grade, resulting in an immunohistochemical staining index. At the cut-point 0.35 the index divided all 157 patients (P=0.0188), and 57 node-positive patients (P= 0.0006) into two groups of different survival. In multivariate analysis (all patients) E-cadherin immunoscore was inferior to mitotic index (SMI) (P=0.0002), but still significant (P=0.0031). Among node-positive patients E-cadherin was even more powerful and superior (P=0.0001) to the still significant SMI (P=0.0023), and E-cadherin immunostaining and the mitotic activity (SMI) combined did not need the support of other prognosticators in the Cox model. CONCLUSIONS: The study suggests that E-cadherin immunostaining can be used efficiently in finding patients with favourable outcome among node-positive patients.

Adult↗
PubMed2002

Proliferation in African breast cancer: biology and prognostication in nigerian breast cancer material.

Three hundred cases of invasive breast carcinoma from the University of Calabar Teaching Hospital, Nigeria were subjected to evaluation of proliferative activity by mitotic counts. The prognostic significance and association with other prognostic factors were evaluated. The mitotic activity was expressed as mitotic activity index (MAI), and standardized mitotic index (SMI). Pearson's correlation and univariate and multivariate Cox's regression were used. The mean follow-up time was 25.9 months. The mean values of SMI and MAI were 42.6 mitotic figures per square millimeter and 30.5 mitotic figures per 10 high-power fields, respectively, and these were much higher than values reported for Europe or other Western countries. The SMI had a positive correlation with tumor size (r = 0.31, P <.0001), histologic grade (r = 0.68, P <.0001), nuclear area (r = 0.45, P <.0001), and negative correlation with fraction of fields with tubular differentiation (FTD; r = -0.56, P = <0.0001). There was no statistically significant difference in the mitotic activity between the postmenopausal and the premenopausal patients. Also, lymph node-positive patients had higher counts than did lymph node-negative patients. Earlier determined grading associated decision thresholds divided the patients into groups of favorable and unfavorable prognosis. However, the statistically optimal thresholds for Nigerian material were different (32 and 92 mitotic figures per square millimeter for SMI). Tumor size of 5 cm, SMI, and MAI were independent prognostic factors. Nigerian breast cancers are high-grade, high-stage, and high-proliferating cancers occurring in a younger population than those of the Western countries. Proliferation is also more active. Evaluation of SMI or MAI can improve the distinction between aggressive and less aggressive variants of breast cancer.

Adolescent↗
PubMed2002

Dependence of DNA-histograms on the sampling techniques in fine needle aspirates of the breast.

48 fine needle aspiration biopsy (FNAB) samples from 25 breast cancer cases, originally used for cytodiagnosis were subjected to DNA cytometry. There were air dried smears stained with the MGG method, and samples stained with HE or PAP stain after 50% ethanol fixation and cytocentrifugation. Different sampling strategies were applied. Four methods were tested: method 1: cell groups measured, method 2: all cells measured, method 3: free cells measured, and method 4: atypical free cells measured. Method 4 showed most often DNA aneuploid histogram patterns, sampling method 1 had the highest number of DNA diploid histogram patterns. Diagnostic approaches may benefit from a sampling method detecting the hiding aneuploid cell population. Grading of neoplasm could potentially benefit from other approaches.

Aneuploidy↗
PubMed2002

Influence of age and prognosis of breast cancer in Nigeria.

OBJECTIVE: To determine the relationship between the age at diagnosis and established prognostic factors of breast cancers in Calabar, Nigeria. Attempts made to assess the prognostic value of age at presentation. DESIGN: Retrospective study of invasive breast cancer seen in Calabar over a seventeen-year period. Pearson's correlation, univariate and multivariate Cox's regression were used. SETTING: University of Calabar Teaching Hospital, Calabar, Nigeria, a referral and teaching hospital. SUBJECTS: Three hundred cases of invasive breast cancer diagnosed between 1983 and 1999 in Calabar, Nigeria. The necessary follow-up data was available for 129 patients. RESULTS: The mean age at diagnosis of breast cancer in Nigeria was 42.7 years (SD 12.2, range 18-85 years). Patients less than 40 years accounted for 39.8% of the total number of patients with infiltrating breast carcinoma. In the whole material (n=300), there was a positive association between age and tumour size (r=0.44, p=<0.0001), stage (r=0.47, p=<0.0001), the degree of necrosis (r=0.21, p=0.0002), histological grade (r=0.11, p=0.0476), MAI (mitotic activity index, r=0.12, p=0.0338), and MNA (mean nuclear area, r=0.17, p=0.0033). The correlation between age and SMI (standardized mitotic index), AI (apoptotic index), SMI/AI ratio, and FTD (fraction of fields showing tubular differentiation) were not statistically significant. The optimal decisive prognostic cut point for age was 33 years (p=0.0064). Age was also a significant prognosticator when used as a continuous variable (p=0.0240). Survival was better in the younger patients. However, in the Cox's multivariate analysis involving SMI, tumour size and age (both as a continuous variable and using the determined cut point of 33 years), the age at diagnosis lacked an independent prognostic value. CONCLUSION: The more advanced nature of breast cancers and the possible more aggressive tumours (reflected by the higher MNA values) in the older patients may explain the poorer survival seen in patients diagnosed at 40 years or above. It is also probable that the lifestyle differences between the two studied age groups may influence the early detection and prompt commencement of therapy. Screening and treatment approaches between the two age groups may differ in view of the differences.

Adult↗
PubMed2001

Epidemiology of basal cell carcinoma of the eyelid in south-western Finland.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumour of the skin in Caucasians. It often appears on the eyelids but there are no population-based studies on the incidence of BCC of the eyelid in Nordic countries. METHODS: The mean annual incidence rates of BCC of the eyelid in the region of South-Western Finland from 1977 to 1997 were calculated. RESULTS: The mean annual incidence (per 100,000 population) of BCC of the eyelid showed a statistically significant increase from 0.82 (in 1977-1979) to 2.88 (in 1995-1997). The incidence of BCC of the eyelid was 0.8 in the age group of 30-49 years and rose significantly with age (P < 0.0005) to the maximum of 17.2 in the age group of 80-89 years. There were no statistically significant differences in the incidence rates of BCC of eyelid between males and females or between urban, semi-urban and rural populations. CONCLUSION: In South-Western Finland the incidence of BCC of the eyelids more than tripled during the years from 1977 to 1997. This may be due to the increase of the elderly population, because the incidence showed a significant increase with age.

Adult↗
PubMed2001

Apoptosis, analysed by means of lamin B detection, correlates with grade of astroglial tumours but not with p27Kip1/retinoblastoma protein expression.

The aim of our study was to correlate apoptosis, assessed by means of lamin B degradation, with grade of tumour and immunohistochemical expression of p27Kip1 and retinoblastoma protein (pRB) in a series of 32 low-grade astrocytomas (LGA) and 43 high-grade astrocytomas (HGA). Determination and analysis of lamin B expression was achieved stereologically with the use of computerised interactive image analysis. The average stereological surface density of the lamin-positive nuclear surface of cells showing evidence of lamin degradation cells was 13.80 mm2/mm3 in LGA and 21.02 mm2/mm3 in HGA. The average range of immunopositivity of p27 and pRB expression was 2.85 and 2.10, respectively, in LGA and 1.80 and 0.88, respectively, in HGA. The rate of apoptosis indirectly correlated with the expression of both p27 and pRB but was not fully significant (P < or = 0.09). Our findings suggest that there may be a loss of function of main cell-cycle regulators and increased uncontrolled cell death in addition to increased cell proliferation in high-grade astrocytomas. Moreover, we believe that the detection of lamin B degradation in astroglial tumours can be an alternative, precise and convenient assay for the detection of a defined set of apoptotic cells. However, before being applied more generally, comparative research should be done on different methods of quantifying apoptosis, with the intent of finding the difference between biologically different methods. Such studies would also be able to find the method associated with the strongest prognostic power.

Apoptosis↗
PubMed2001

Nucleolar morphometry in fine needle aspiration biopsies of the prostate.

OBJECTIVE: To find efficient morphometric nucleolar features for distinguishing different prostatic atypia groups in fine needle aspiration biopsies. STUDY DESIGN: A computerized interactive morphometry program was used to outline nucleoli of prostate cells. The samples were divided into three groups: group 1 (definitely benign [n = 10] and atypical but benign [n = 13]), group 2 (moderately atypical [n = 11] or highly suspicious [n = 13]) and group 3 (definitely malignant [n = 17]). RESULTS: The analysis revealed a difference in the number of nucleoli between definitely benign samples and other atypia groups but not between the latter. Nucleolar size features were best in distinguishing between atypia groups. The sample-associated mean size features were more powerful than cell group-associated size features. CONCLUSION: The sample-associated mean area, defined from cells selected by an experienced cytologist, if larger than 2 micron 2, was strongly associated with definitely malignant samples. The same was true for the largest nucleolar area if larger than 5.0 micron 2. Morphometric nucleolar size features appeared efficient in distinguishing between definitely malignant and other samples.

Adenocarcinoma↗