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Jan F Silverman

Publications and source records attributed to Jan F Silverman.

At least 19 recordsLinked to original sources
PubMed2006

Lymphatic microvessel density as prognostic marker in colorectal cancer.

Lymph node metastases is an important prognostic indicator for disease progression and crucial for therapeutic strategies in the work-up of colorectal carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular endothelial growth factor (VEGF) expression as predictive markers for the risk of lymph node metastasis and their relation to other prognostic parameters in colorectal carcinoma. Resected colorectal carcinomas from 90 patients were examined, including 30 patients without lymph node metastases, 30 with only lymph node metastases, and 30 with liver metastases. Cases were immunostained for CD31, D2-40, and VEGF. Positivity stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at x 400 field (=0.17 mm2). Intensity of staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel density demonstrated significant correlation with CD31 counts (20+/-9 vs 18+/-6/0.17 mm2 field, P<0.05) and VEGF expression (P<0.01). VEGF was expressed in 61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients, which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90). There was a positive significant correlation of D2-40, CD31 counts, and VEGF expression with the presence of lymphovascular invasion and lymph node metastases (P<0.05). D2-40 lymphatic microvessel density correlated significantly with depth of invasion (pT), positive vascular pedicle lymph nodes and liver metastases (P<0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic significance with positive correlation with lymphovascular invasion, pT, and metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the detection of lymphatic invasion relative to H&E staining and the endothelial marker, CD31.

Adult↗
PubMed2006

Critical diagnoses (critical values) in anatomic pathology.

Similar to critical values in clinical pathology, occasional diagnoses in surgical pathology and cytology may require urgent contact of the physician to facilitate rapid intervention or treatment. However, there are no established critical value (critical diagnosis) guidelines in anatomic pathology. As discussed herein, the Association of Directors of Anatomic and Surgical Pathology (ADASP) believes that establishing anatomic pathology critical diagnosis guidelines represents a practice improvement and patient safety initiative. The ADASP also recognizes that a generic anatomic pathology critical diagnosis guideline such as this should only be used as a template because the list needs to be customized at each individual hospital after consultation with relevant clinical services. Based on surveys of the membership of the ADASP, this document provides examples of possible critical diagnoses in anatomic pathology.

Diagnostic Errors↗
PubMed2006

Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology.

Neoplastic progression is characterized by clonal expansion of tumor cells associated with accumulation of mutational damage. The timing of mutation acquisition could be of value in distinguishing preneoplastic conditions from early and advanced cancer as well as characterizing tumor aggressiveness and treatment response. Using quantitative methods applied to microdissected cell clusters selected according to cytomorphologic features, we sought to demonstrate the feasibility and efficacy for determining the time and course of mutation accumulation in pancreatobiliary cytology specimens. In all, 40 pancreatic duct and 21 biliary brushing cytology specimens were retrieved from the cytology database. Xylene-resistant markings were placed on the slide underside and coverslips removed. Clusters of benign, atypical and malignant cells were manually microdissected and DNA extracted. Mutations (allelic imbalance) (loss of heterozygosity) were quantitatively determined for a broad panel of 15 markers (1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q) as well as point mutation in K-ras-2 using PCR/capillary electrophoresis. Time course was based on earlier mutations having a higher proportion of mutant DNA for a particular marker. The descending frequency of detectable mutational involvement in pancreatic cytology was K-ras-2 point mutation (58%), 3p25-26 and 17q21 (35%), 5q23 (33%), 1p36 (28%), followed by the remaining molecular markers. The descending frequency of mutational content in bile duct cytology was 17p13, 1p36, 3p25-26, and 5q23 followed by remaining molecular markers. K-ras-2 point mutation was not seen in bile duct specimens. While there was overlap in the spectrum of mutational markers in pancreatic duct and biliary brushing cytology, the temporal profile was significantly different (P<0.001). Pancreatic and biliary neoplasia progression involves distinct subset of accumulated defined mutations. Determination of timing of the mutational damage in cytologic material could be incorporated in the work-up and help in making a more definitive diagnosis of malignancy in pancreatobiliary cytology specimens.

Biliary Tract Neoplasms↗
PubMed2006

Critical values in cytology.

The concept of critical values (CVs) is well established in clinical pathology, and has only recently been suggested in surgical pathology. To evaluate CVs in cytology, we reviewed 2,000 cytology reports at two large academic medical centers. Cases considered CV included unexpected malignancy, disagreement between immediate interpretation and final diagnosis in fine-needle aspirations (FNAs), and evidence of microorganisms in non-gynecology (non-GYN) and FNA specimens. We identified 52 CV cases (2.6%), including 0.25% (1/400) GYN, 1.88% (15/800) non-GYN, and 4.5% (36/800) FNA. Most of these (42 cases) were unexpected malignancies. Documentation of physician notification was present in 30 out of 52 cases. We also did a survey with 22 cytopathologists and 13 clinicians at large academic medical centers. The participants were asked to rate 18 different possible CVs from 1 to 3 as follows: (1) no phone call necessary, (2) phone call within 24 hr, (3) phone call as soon as possible (ASAP). Participants could also list additional diagnoses they believed constituted a CV. Most respondents agreed on the need for a phone call ASAP in many situations, and important additional CV cases were suggested. We suggest that a consensus conference of leaders in anatomic pathology and clinicians might prove useful to propose guidelines for CVs in cytology.

Cytodiagnosis↗
PubMed2006

The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement.

Differentiating malignant mesothelioma (MM) from pulmonary carcinoma in pleural fluid cytology can be challenging. Recent studies have suggested that D2-40, a novel lymphatic marker, may be a useful marker for mesothelial differentiation in surgical specimens. However, there are no available data regarding its utility in effusion cytology specimens. We investigated the utility of D2-40 in pleural fluid cytology in differentiating MM from pulmonary carcinomas. Twenty cases of pleural effusion smears of surgically confirmed MM with their corresponding cell blocks were retrieved from the database of the hospital computer system. We also included 10 cases of metastatic pulmonary adenocarcinoma (PA) and 10 cases metastatic pulmonary squamous cell carcinoma (PSCC) involving the pleural fluid. Cell blocks were formalin-fixed, paraffin embedded, and immunostained for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40. Cases were scored as negative (<5% positivity) or positive (>5% moderate/strong positivity). The positive rates for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40 were as follows: MM (0/20), (0/20), (17/20), (18/20), (19/20), (17/20), for PA (8/10), (0/10), (3/10), (0/10), (0/10), (0/10), and for PSCC (1/10), (10/10), (6/10), (10/10), (0/15), (0/10). The staining pattern for D2-40 was characterized by thick membranous staining. Diffuse cytoplasmic staining by D2-40 was seen in 2 cases of pulmonary carcinoma, counted as negative. Our study showed that in differentiating MM from PA, CK5/6, WT-1, and D2-40 have high specificity and sensitivity for MM. Although calretinin is a sensitive IHC marker for MM, it is not specific since it stained 30% of PA. Conversely, to differentiate between MM and PSCC, p63 and WT-1 are the best available markers. We recommend a panel of CK5/6, p63, D2-40, and WT-1 to differentiate MM from pulmonary carcinomas in effusion cytology specimens.

Aged↗
PubMed2006

The diagnosis of malignancy in effusion cytology: a pattern recognition approach.

This review presents a pattern recognition approach for the diagnosis of malignant effusions. The cytomorphologic features of reactive mesothelial proliferation, mesothelioma and metastatic carcinoma are presented. In addition, the role of ancillary studies in challenging cases and the importance of integrating clinical findings are stressed. An algorithmic approach to the workup of serous effusions as well as pitfalls for false-positive diagnosis are discussed.

Adenocarcinoma↗
PubMed2006

Critical diagnoses (critical values) in anatomic pathology.

Similar to critical values in clinical pathology, occasional diagnoses in surgical pathology and cytology may require urgent contact of the physician to facilitate rapid intervention or treatment. However, there are no established critical value (critical diagnosis) guidelines in anatomic pathology. As discussed herein, the Association of Directors of Anatomic and Surgical Pathology (ADASP) believes that establishing anatomic pathology critical diagnosis guidelines represents a practice improvement and patient safety initiative. ADASP also recognizes that a generic anatomic pathology critical diagnosis guideline such as this should be used only as a template because the list needs to be customized at each individual hospital following consultation with relevant clinical services. Based on surveys of the membership of the ADASP, this document provides examples of possible critical diagnoses in anatomic pathology.

Female↗
PubMed2006

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women.

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.

Aged↗
PubMed2006

Critical values in anatomic pathology.

Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.

Diagnostic Errors↗
PubMed2005

The value of epithelial membrane antigen expression in separating benign mesothelial proliferation from malignant mesothelioma: a comparative study.

Differentiating reactive mesothelial (RM) proliferation from malignant mesothelioma (MM) can be cytologically challenging. There have been discordant studies reporting the value of epithelial membrane antigen (EMA) in differentiating RM from MM. In this study, we investigated the expression of two different clones of EMA in RM and MM. Twenty cases of pleural effusion smears of RM and 20 cases of MM with their corresponding cell blocks were retrieved from the hospital computer system. Diagnosis of MM was confirmed by surgical decortication or pneumonectomy with immunostaining studies and/or electron microscopy. Cases of RM were confirmed by clinical history and histology. Cell blocks were formalin-fixed, paraffin-embedded, and immunostained for EMA clone Mc5 and EMA clone E29. The positive rates for clone Mc5 were 14/20 (70%) for MM and 12/20 (60%) for RM and EMA clone E29 were 15/20 (75%) for MM and 0/20 (0%) for RM. The sensitivity and specificity for EMA clone Mc5 were 70 and 40%, respectively. For EMA clone E29, the sensitivity and specificity were 75 and 100%, respectively. In conclusion, both RM and MM immunostained for EMA clone Mc5, indicating that it is not a reliable immunocytochemical marker for differentiating RM from MM. EMA clone E29 was negative in all cases of RM and positive in 75% of MM and therefore is a reliable immunocytochemical marker for differentiating RM from MM.

Aged↗
PubMed2005

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma.

Endoglin (CD105), a member of transforming growth factor beta1 receptor complex, has been shown to be a more useful marker to identify tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor (VEGF) expression as possible prognostic markers in esophageal adenocarcinoma. Surgical specimens from 75 patients with esophageal adenocarcinoma treated with esophagectomy were immunostained for endoglin, CD31, and VEGF. We also included 10 cases of Barrett's esophagus with high-grade dysplasia and 10 cases with Barrett's esophagus low-grade dysplasia. Positively stained microvessels (MVs) were counted in hot spots at magnification of x400. Results were expressed as the highest number of MV identified. For VEGF, intensity of staining was scored on 3-tiered scale. Endoglin demonstrated significantly more vessels than the CD31 (mean, 28.9 +/- 13.2 versus 19.0 +/- 9.4, P < .001). Both endoglin and CD31 MV counts showed significant correlation with stage of the disease (r = 0.59, P < .001; r = 0.52, P < .001, respectively) and patient survival (log rank P < .01). Only endoglin MV count was significantly correlated with the presence of angiolymphatic invasion (r = 0.34, P < .05) and lymph node (LN) metastases (r = 0.48, P < .001). Univariate analysis showed that endoglin MV count is an independent prognostic factor. Endoglin showed a significant increase in MV count in Barrett's esophagus with high-grade dysplasia when compared with Barrett's esophagus low-grade dysplasia (P < .01), whereas CD31 did not show any significant difference. VEGF was expressed in 48 (64%) of 75 cases of adenocarcinoma and was significantly correlated with angiolymphatic invasion, LN metastases, and survival. In conclusion, endoglin is a specific and sensitive marker for tumor angiogenesis. Endoglin staining also showed prognostic significance with positive correlation with the presence of angiolymphatic invasion, LN metastases, tumor stage, and survival.

Adenocarcinoma↗
PubMed2005

Follow-up surgical excision is indicated when breast core needle biopsies show atypical lobular hyperplasia or lobular carcinoma in situ: a correlative study of 33 patients with review of the literature.

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.

Adult↗
PubMed2004

Diagnostic utility of CDX-2 expression in separating metastatic gastrointestinal adenocarcinoma from other metastatic adenocarcinoma in fine-needle aspiration cytology using cell blocks.

BACKGROUND: CDX-2 gene is a transcription factor that is involved in the proliferation and differentiation of intestinal epithelial cells. Recent studies have shown that CDX-2 could be used as an immunohistochemical marker to differentiate metastatic gastrointestinal adenocarcinoma from other metastatic adenocarcinomas in surgical pathology. The objective of the current study was to investigate the diagnostic value of CDX-2 to separate metastatic gastrointestinal adenocarcinoma from other metastatic adenocarcinomas in fine-needle aspiration cytology (FNAC). METHODS: Sixty-two FNAC specimens of metastatic adenocarcinomas with corresponding cell blocks were retrieved from the hospital computer system. There were 22 specimens of metastatic gastrointestinal adenocarcinoma, 20 specimens of metastatic pulmonary adenocarcinoma, and 20 specimens of metastatic adenocarcinomas from other sites, including 10 from the breast, 3 from the ovaries, 4 from the pancreas, and 3 from the prostate. Radiology and histologic evaluation confirmed all cases. Sections were immunostained for CDX-2 and thyroid transcription factor-1 (TTF-1) using a heat-induced epitope retrieval technique. RESULTS: In metastatic gastrointestinal adenocarcinoma, CDX-2 demonstrated positive nuclear staining in 19 of 22 specimens (86%). Other specimens of metastatic adenocarcinoma were negative for CDX-2. TTF-1 expression was detected in 0%, 80%, and 0% of metastatic gastrointestinal adenocarcinoma, pulmonary adenocarcinoma, and other adenocarcinoma specimens, respectively. CONCLUSIONS: The results of the current study demonstrated that CDX-2 is a sensitive and a specific marker to separate metastatic gastrointestinal adenocarcinoma from other metastatic adenocarcinomas in FNAC specimens.

Adenocarcinoma↗
PubMed2004

Intracellular patterns of Her-2/neu, ras, and ploidy abnormalities in primary human breast cancers predict postoperative clinical disease-free survival.

PURPOSE: In an earlier study, the presence of aneuploidy, Her-2/neu overexpression, and ras overexpression in the same cells (triple-positive cells) was of prognostic significance (P < 0.015) in 91 patients with localized breast cancer (median follow up, 32 months). Here, we present results involving a larger group of patients with longer follow-up. EXPERIMENTAL DESIGN: Fixed cell suspensions prepared from primary tumors of 189 patients with early breast cancer were studied prospectively by multiparameter flow cytometry. Correlated intracellular fluorescence-based measurements of cell DNA content and Her-2/neu and ras protein were obtained on each of >2000 cells in each tumor. Intracellular combinations of abnormalities in these measurements were correlated with subsequent patient disease-free survival (DFS). Median time on study was 54 months (range, 7-128 months). RESULTS: DFS of patients with > or = 5% triple-positive tumor cells was shorter than those who did not meet this criterion (P = 0.004). The difference remained statistically significant after accounting for nodal status, tumor size, and each of the component abnormalities (P = 0.006). Node-negative patients whose tumors had fewer than 2 abnormalities/cell had an especially favorable clinical course, with a 5-year DFS of 96% (lower confidence bound, 86%). CONCLUSIONS: Patterns of accumulated intracellular molecular abnormalities in cells of primary human breast cancers are predictive for subsequent DFS independently of the abnormalities themselves taken individually.

Adult↗
PubMed2004

Diagnostic value of HepPar1, pCEA, CD10, and CD34 expression in separating hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration cytology.

Differentiating primary and metastatic hepatic malignancies can be diagnostically challenging in fine-needle aspiration cytology (FNAC). We compared four immunohistochemical (IHC) markers, pCEA, CD10, HepPar1, and CD34, in differentiating hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) in FNAC specimens. Sixty cases of liver FNAC with their corresponding cell blocks were retrieved from the hospital computer system, including 30 HCC and 30 MC (15 colon, 10 breast, and 5 pancreas). The diagnoses were confirmed by clinical follow-up and surgical resection or core needle biopsy. The direct cytologic smears were air-dried and Diff-Quik-stained, and alcohol-fixed and Papanicolaou-stained. Cell block sections from the aspirates were immunostained for pCEA, CD10, HepPar1, and CD34. IHC on cytologic smears for HCC was performed on 10 cases and compared with the cell block results. In HCC, CD10, and pCEA demonstrated the characteristic canalicular staining in 23/30 (77%) and 24/30 (80%) of the cases, respectively; however, none of the MC showed a canalicular staining pattern. HepPar1 was positive in 26/30 (87%) of the HCC cases and one MC. CD34 stained sinusoidal endothelial cells in 27/30 (90%) cases of HCC and six MC. Our results demonstrate that the canalicular staining pattern for CD10 and sinusoidal staining pattern of CD34 are very specific, in addition to the high specificity and sensitivity of HepPar1 for HCC. Cell blocks were more informative in demonstrating the characteristic architecture and immunostaining pattern of the malignancy than the cytologic smears. An IHC panel consisting of pCEA, CD10, HepPar1, and CD34 is useful for confirming HCC in FNAC of the liver.

Antigens, CD34↗
PubMed2004

Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung.

Thyroid transcription factor 1 (TTF-1) is a diagnostic immunohistochemical marker for primary pulmonary neoplasms, but its utility as a prognostic marker is not well established. Surgical specimens from 100 cases of pulmonary adenocarcinoma were retrieved from the hospital computer system, including 50 cases of conventional adenocarcinoma (CA) and 50 cases of bronchioloalveolar adenocarcinoma (BAC) (32 nonmucinous type and 18 mucinous type). Representative sections were immunostained for TTF-1. Positive immunohistochemical study was correlated with other prognostic parameters. In the CA group, strong or moderate TTF-1 expression was seen in 30 of 50 (60%) patients and was associated with significantly better survival compared with those patients having weak staining (7 cases; 14%) or negative staining (13 cases; 26%) (P <0.01; log-rank test). Spearman and Pearson's correlation showed no significant correlation between TTF-1 expression and tumor grade, size, recurrence, or vascular invasion; therefore, TTF-1 was considered an independent predictor of survival. In the BAC group, TTF-1 was strongly expressed in 34 of 50 cases (68%) and was negative in 16 of 50 cases (32%), including 14 mucinous BACs. Although TTF-1 immunoreactivity was not statistically associated with good survival in BAC patients, those patients with strong immunohistochemical expression showed a trend toward longer survival. Our results indicate that TTF-1 positivity is an independent predictor of better survival, especially in patients with CA. Mucinous and nonmucinous BACs exhibit disparate staining patterns with TTF-1, with nonmucinous BAC demonstrating greater positivity. Although nonmucinous BAC patients showing strong positive staining had longer survival, the difference was not statistically significant, which is probably related to the overall good survival of patients with early-stage BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer.

Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at x 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (P<0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (P<0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (P<0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.

Adult↗