Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors

While tumors of dendritic cell lineage may have overlapping histomorphologic features, most but not all cases can be classified using an immunohistochemical panel, including CD21, CD23, CD35, CD1a, and S-100. Based on observations that clusterin is expressed in benign follicular dendritic cells, clusterin expression in 32 dendritic cell tumors was evaluated. Diffuse strong staining for clusterin was seen in 12 of 12 follicular dendritic cell tumors. Two of these cases were negative for traditional markers (CD21, CD23, CD35); they were classified based on characteristic ultrastructural features. Three of 6 interdigitating dendritic cell tumors were negative for clusterin and 3 showed focal weak positivity. Clusterin staining in Langerhans cell histiocytosis ranged from negative (6 of 14) to weak/moderate (8 of 14). Follicular dendritic cell tumors behaved as benign tumors or low-grade sarcomas. Interdigitating dendritic cell tumors demonstrated a widely variable behavior, ranging from benign to rapidly fatal disease. Based on this initial study, strong clusterin staining supports a diagnosis of follicular dendritic cell tumor. Thus, staining for clusterin is useful in classification of dendritic cell tumors, particularly when the more common markers of follicular dendritic cells are not expressed.     

Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung

Objective: To analyze the prognostic value of hypoxia-inducible factor-1 (HIF-1) alpha expression and its correlation with clinicopathologic variables and the expression of vascular endothelial growth factor-A and -C in patients with lung adenocarcinomas of small size. Methods: The expression of hypoxia-inducible factor-1 alpha was immunohistochemically determined in 78 cases of small-sized adenocarcinoma (maximum dimension ≤ 2 cm) using antibody against a recombinant protein corresponding to amino acids 575–780 of hypoxia-inducible factor-1 alpha. Data regarding patient survival, clinicopathologic factors, and immunohistochemical studies of vascular endothelial growth factors were also collected. Results: Strong expression of hypoxia-inducible factor-1 alpha was observed in 23 of 78 cases; absent or minimal expression was found in the localized bronchioloalveolar carcinomas. Strong expression of hypoxia-inducible factor-1 alpha was significantly higher in cases with vascular invasion, lymph node involvement, and vascular endothelial growth factor-A expression. The 5-year survival rate was 63.2% if expression of hypoxia-inducible factor-1 alpha was strong and 85.1% if expression was weak (p < 0.05). Conclusion: Immunohistochemical staining of HIF-1 alpha, along with examination of metastatic potential via vascular pathways, may be valid defining a subpopulation of patients with small-sized adenocarcinoma of the lung whose tumors have aggressive angiogenesis potential.     

Localized renal-cell carcinoma: detection of abnormal cells in peritumoral tissue

Summary To spare organ function, partial resection of early diagnosed renal-cell carcinoma (RCC) is applied for well-localized and small-volume RCC with increasing frequency, although recurrence of the tumor in the same kidney is occasionally observed. The aim of the present study was to establish objective prognostic parameters that would allow the selection of tumors suitable for an organ-saving procedure. Of the 160 patients undergoing a radical nephrectomy, 67 were included in this study. In 7/45 patients with lymph-node dissection (15.6%), clinical staging revealed a false-negative lymph-node status. By means of conventional histopathology, multifocality could be demonstrated in 2/67 patients (3%); in 1/67 patients (1.5%), the ipsilateral adrenal gland was unexpectantly tumor-involved. Both tumor tissue and normal peritumoral tissue were examined for the presence of premalignant and tumor cells on the basis of DNA ploidy and of the expression of the tumor-associated G250 antigen, which is specifically expressed at the surface of renal cancer cells. In 40/67 (59.1%) peritumoral tissue specimens, cells with an abnormal DNA content could be observed using automated image analysis. In 12/67 cases (18%), cells obtained from peritumoral tissue also showed an aneuploid DNA histogram; 4/67 (6%) had a tumor-correlated DNA ploidy. Additionally, 38/67 (56.9%) of these tissues, histopathologically classified as normal, contained cells expressing the G250 antigen. These observations were independent of the stage or histological grade of the tumor. These data indicate that classic pathological parameters for tumor staging are insufficient for the detection of multifocality, occurring in more than 15% of cases. Additionally, it was shown that examination of tissue adjacent to the RCC allowed a specific detection of abnormal cells revealing abnormal ploidy or altered expression of tumor-associated antigens as compared with normal renal tissue in nearly 60% of cases investigated. The clinical relevance of this observation remains to be determined.     

Clinical Implication of CXCL12 Expression in Gastric Cancer

PURPOSE: Recent research has revealed that tumor cells expressing chemokine receptors have a crucial impact on patient survival. However, there is no information regarding chemokine expression in gastro-intestinal cancer. This study immunohistochemically investigated CXCL12 expression in gastric cancer and evaluated its association with clinical factors, including patient prognosis. METHOD: A total of 185 gastric cancer patients receiving curative gastrectomy were assessed. CXCL12 expression was evaluated by immunohistochemical analysis. Tumors with CXCL12-positive cancer cells were regarded as CXCL12 positive, and according to the degree of CXCL12 expression, patients were divided into three groups (weak, 31 cases; moderate, 27 cases; strong, 20 cases). Correlations between CXCL12 expression and clinical factors in gastric cancer were then determined. RESULTS: CXCL12 was found in the cellular membrane of cancer cells. Seventy-four of 185 patients were classified into the CXCL12-positive group. Patients were divided into three groups according to the positivity of CXCL12 expression. Significant associations between CXCL12 and lymph node metastases (p < 0.05), depth of invasion (p < 0.01), lymphatic invasion (p < 0.01), tumor diameter (p < 0.05), and clinical stage (p < 0.01) were seen. Univariate analysis revealed that the CXCL12-positive group had significantly poorer surgical outcome than the CXCL12-negative group (p < 0.01). Multivariate analysis revealed CXCL12 to be an independent prognostic factor in gastric cancer (p = 0.02). CONCLUSION: Cancerous CXCL12 positivity was determined to be an independent prognostic factor in gastric cancer, with CXCL12-positive gastric cancer showing more-aggressive behavior. Autocrine CXCL12 secretion from tumor cells may activate CXCR-4 on the tumor cells, which may be related to of the viability of distant metastases.     

Survivin在胆管癌表达与预后的关系

目的 探讨胆管癌患者中Survivin的表达在提示预后中的作用.方法 48例手术切除的胆管癌标本,应用免疫组织化学技术(SP法)检测Survivin基因在48例胆管癌中的表达.Survivin的表达分别描述为阴性或弱阳性和强阳性.结果 Survivin在胞质和细胞核表达例数分别为26例和22例患者.细胞质中强阳性表达为12例,而细胞核强阳性表达的则有8例.细胞核强阳性表达的患者平均存活期为10个月,明显低于弱阳性表达的患者(19个月,P＜0.05).Cox比例风险率模型的多因素分析方法 证实存在2个独立的预后因素:Survivin细胞核表达(P＜0.05)和远处转移(P＜0.05).结论 胆管癌中Survivin的细胞核表达可提示较差的预后.     

DNA ploidy and the S-phase fraction and their prognostic significance in gastrointestinal tumors

The prognostic significance of nuclear DNA ploidy patterns and the S-phase fraction (labeling index; IL) were evaluated in 365 gastrointestinal tumors, and in 62 of them a combined analysis of DNA ploidy and the SPF was performed. For accurate evaluation, we used fresh frozen specimens, and we classified the ploidy pattern into 6 types; 1. diploid, 2. DS (diploid + high LI), 3. Notch, 4. Shoulder, 5. Tetraploid and 6. Aneuploid. Type 1 or type 2 tumors were classified as diploid, and the others were classified as aneuploid. In 103 cases of gastric cancer and 101 colon cancers due to the short observation period, but in 46 patients with operable primary liver cancer, a significant difference was observed. A high average of LI was detected in colon cancer (approximately 13%), but no relationship between LI and the ploidy pattern was found. This indicates that the LI may become an independent prognostic factor, and that the combined assay of DNA ploidy and the LI may offer a more precise evaluation of the malignant potential of gastrointestinal tumors.     

Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience

Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast cancer. In this first-ever study, we investigated the role of nine prognostic markers' expression (estrogen receptor [ER], progesterone receptor [PR], p53, C-erbB-2, epidermal growth factor receptor [EGFR], cathepsin D [CD], proliferating cell nuclear antigen [PCNA], DNA ploidy, and S-phase fraction [SPF]) and disease outcome in IBC cases compared with the control group. A case control study of IBC was conducted on 40 test cases with two controls per case matching age, grade, and number of axillary lymph nodes sampled. During 7 years of this study, 10% of all patients with breast cancer had IBC. In this study, 84% of IBC cases showed positive axillary lymph nodes compared with 63% in control group. The expression of nine prognostic markers, that is, ER, PR, p53, C-erbB-2, EGFR, CD, PCNA, SPF, and DNA ploidy, was studied by immunohistochemistry and flow cytometry. Hormone receptor status showed an inverse correlation (p < 0.05). Among p53, C-erbB-2, EGFR, and CD in the IBC group, only p53 showed a significant correlation, with 70% positivity in IBC versus 48% positivity in the control group (p < 0.05). Much higher SPF and PCNA positivity was seen in the IBC group compared with the control group (p < 0.05). DNA ploidy also showed a significant correlation compared with the control group (p < 0.05). After a median follow up of 18 months, median overall survival in the IBC group was 1.8 years (range 0.6–5.8 years) compared with 3.0 years (range 2.5–7.0 years), with a p value of 0.0001.     

Clinical importance of c-Met protein expression in high grade astrocytic tumors

The clinical importance of the expression of c-Met protein, the receptor of hepatocyte growth factor/scatter factor, was evaluated in neuroepithelial tissue tumors. c-Met immunohistochemistry was performed using the streptavidin-biotin-peroxidase complex method with anti-c-Met polyclonal antibody. Specimens were classified as c-Met negative (< 30%) or c-Met positive (> or = 30%) according to the proportion of immunopositive cells under microscopic examination. All c-Met-positive cases occurred in high grade astrocytic tumors, not in other neuroepithelial tissue tumors. Most c-Met-positive astrocytic tumors were classified histologically as high grade tumors. Epidermal growth factor-receptor (EGFR) and MIB-1 immunohistochemistry were also performed for high grade astrocytic tumors. Survival analysis was performed for patients with these tumors with variables including c-Met positivity, EGFR positivity, and MIB-1 labeling index. Positivity of c-Met was independent from EGFR positivity and MIB-1 labeling index, and the c-Met-positive group showed a significant shorter survival (p < 0.05). c-Met immunopositivity may be a parameter of biological aggressiveness in high grade astrocytic tumors. Examination of c-Met expression in astrocytic tumors provides significant clinical information, especially as a prognostic factor.     

Prognostic Significance of the Combination of Biological Parameters in Breast Cancer

To evaluate whether the combination of biological parameters increases their prognostic value, the expression of epidermal growth factor receptor (EGFR), DNA ploidy, and estrogen receptor (ER) status were analyzed on 998 patients with breast cancer. Poor findings for each biological parameter were positive for EGFR, aneuploid for DNA ploidy, and negative for ER. According to the number of poor findings in these three parameters, the groups with none (309 cases), one (377 cases), two (161 cases), and three (151 cases) poor findings were classified. A significant ( P < 0.0001) difference was found in the disease-free survival (DFS) among the four groups. A multivariate analysis indicated the combination of three biological parameters to be an independently significant factor for DFS, while the relative risk gradually increased as the number of poor findings increased. In conclusion, the present study indicated a gradual increase in the prognostic significance as the number of combined biological parameters increased.     

Aberrant expression of membranous carbonic anhydrase IX (CAIX) is associated with unfavorable disease course in papillary and clear cell renal cell carcinoma

Objective

Antibodies against carbonic anhydrase IX (CAIX) are often part of immunohistochemical panels used to assist renal cell cancer (RCC) subtyping. This study was undertaken to determine, whether assessing CAIX expression levels could provide additional prognostic information.

The prognostic value of inducible nitric oxide synthase in local prostate cancer

OBJECTIVE: To compare the clinical and histological data from patients with prostate cancer with the results of the immunohistochemical analysis of inducible nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS. PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD 6.1) with local prostate cancer treated by radical prostatectomy in two Finnish hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical method was used to detect the expression of iNOS in these specimens, and the expression graded according to staining intensity as none, weak or strong. RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of the patients, respectively, and one specimen was negative for iNOS. Strong expression of iNOS was related to high a preoperative prostate specific antigen (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal status, grade, seminal vesicle or capsular invasion, surgical margin status, perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of cancer cells. A PSA failure was detected in 29 patients but was not predicted by iNOS expression. A Cox multivariate analysis showed that surgical margin positivity, seminal vesicle involvement and number of tumour infiltrating lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was related to a high pT classification and the preoperative PSA level but not to other established prognostic factors; iNOS expression was not a predictor of PSA failure in patients with local prostate cancer.     

CD44 loss in gastric stromal tumors as a prognostic marker

BACKGROUND: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. DESIGN: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. RESULTS: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression > 2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression < or = 2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression < or = 2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. CONCLUSION: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.     

Combination of blood group ABH antigen status and DNA ploidy as independent prognostic factor in transitional cell carcinoma of the urinary bladder

The prognostic value of DNA ploidy and blood group (ABH) antigen reactivity was studied in a consecutive retrospective study of 230 patients with primary transitional cell carcinoma of the urinary bladder. In 195 cases the DNA ploidy and ABH reactivity could be assessed in paraffin-embedded tissue. Early progression (in the first 3 years) occurred in 2% of the patients with diploid ABH positive tumours and in 31% of those with aneuploid ABH negative tumours. The 5-year survival rates corrected for intercurrent mortality were 95 and 56% respectively. In a Cox multivariate analysis, T category, age at diagnosis and histological grade emerged as significant independent prognostic indicators of bladder cancer death, whereas ABH reactivity and DNA ploidy had no significant independent value. However, if the combination of ABH reactivity and DNA ploidy was included in the Cox model, this and T category were independent predictors. When this Cox model was applied to assess the risk of progression, the only independent prognostic factor was the combination of ABH reactivity and DNA ploidy.     

Expression of neuropeptides in normal and abnormal appendices

BACKGROUND/PURPOSE: Increased neuroproliferation in the appendix associated with an increase in substance P (SP), vasoactive intestinal polypeptide (VIP), and growth-associated protein-43 (GAP-43) has been documented in appendices of adults with acute right lower quadrant (RLQ) abdominal pain and absence of gross or histologic signs of appendiceal inflammation. The authors tested whether these findings were present in children with RLQ pain and a normal appendix. METHODS: Immunohistochemistry staining of paraffin-embedded appendices was performed with GAP-43, VIP, and SP. The positive control group included appendices with acute inflammation (group I, n = 5); the negative control group included appendices removed incidentally (group II, n = 5); and the experimental group included appendices from children suspected to have acute appendicitis without histologic signs of inflammation (group III, n = 9). RESULTS: Group I: VIP was strongly expressed in the nerve plexuses. The lamina propria and muscularis showed absent or minimal VIP expression. SP staining was strong in all plexuses and was moderate to strong in the muscularis. SP expression in the epithelium and lamina propria was difficult to quantify secondary to inflammation. Group II: VIP expression was essentially undetectable in the epithelium, lamina propria, and muscularis, and was moderate in the nerve plexuses. Mild SP staining was detected in the nerve plexuses of most specimens, and absent to mild staining was found in the epithelium and muscularis. However, one specimen strongly expressed SP in all layers. Group III: VIP expression was moderate to strong in the lamina propria and muscularis of nearly all specimens, and strong expression was found in all nerve plexuses. All but one specimen strongly expressed SP in plexuses. There was moderate to strong expression of SP in the epithelium, lamina propria, and muscularis in over 50% of specimens. The immunostaining for GAP-43 was very weak and nonspecific and did not help discriminate between the 3 study groups. CONCLUSIONS: Increased neuroproliferation in the lamina propria and muscularis was evident in patients with abdominal pain and normal appendices compared with appendices removed incidentally. The VIP and SP expression in these patients was similar or higher than that observed in patients with acute inflammation on histology.     

Ezrin expression in prostate cancer and benign prostatic tissue

BACKGROUND: The membrane-linking protein ezrin is highly expressed in several types of human cancers and correlations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown. However, such studies have not yet been done on human prostate cancer. This study assesses ezrin protein expression in a series of clinical specimens. METHODS: Immunohistochemical analysis was used to characterize patterns of ezrin expression in prostatic carcinoma and benign epithelium in 103 radical prostatectomy specimens. Ezrin immunoreactivity (IR) was scored 0 to 3 (absent, weak, moderate or strong staining). Agreement between three independent observers was calculated. RESULTS: Ezrin IR in prostate cancers was moderate or strong in 70% of specimens while negative or only weakly positive in benign epithelium. Interobserver agreement of IR score was substantial (mean weighted kappa 0.70, range 0.67-0.73). Ezrin expression correlated with Gleason score (p=0.016) and seminal vesicle invasion (p=0.006) but not with extraprostatic extension or margin status. No correlation with biochemical recurrence after prostatectomy was found (p=0.19). Urothelial and squamous metaplasia invariably showed moderate or strong ezrin expression. Epithelium of seminal vesicles and ejaculatory ducts was always intensely positive. CONCLUSION: Ezrin was expressed in the majority of prostate cancers and correlated with adverse prognostic factors. Interestingly, high levels of ezrin IR were observed in benign metaplastic epithelium and in seminal vesicles.     

细胞黏附、多药耐药及细胞增殖在T1G3型浅表膀胱癌近期复发中的作用

目的　研究细胞黏附、多药耐药及细胞增殖在浅表膀胱癌近期复发中的作用 ,探讨三者的临床预测价值。　方法　对 10 0例浅表膀胱癌患者进行回顾性随访 ,同时用免疫组化法检测首次术后标本中E cad、P gp、Ki 6 7的表达情况。　结果　E cad、P gp的阳性表达率分别为 4 3 2 %和14 4 % ,而PI的平均值为 2 2 1%。E cad表达随复发次数增加而减弱 (P <0 0 5 ) ,P gp表达和PI值随复发次数增加而增高 (P <0 0 5 )。T1G3 型患者与非T1G3 型患者间 ,E cad表达、P gp表达及PI值差异均有显著性 (P <0 0 5 )。E cad表达与P gp表达、PI值之间均呈显著性负相关。　结论　黏附性低、耐药性强和增殖旺盛是促使T1G3 型浅表膀胱癌近期复发的主要因素 ,同时也是导致T1G3 肿瘤易复发、高恶性度的内在原因。在上述过程中 ,三者可能相互影响。     

DNA image cytometric analysis of differentiated thyroid adenocarcinoma specimens.

A total of 117 differentiated thyroid adenocarcinomas that had been removed by total thyroidectomy were studied. Seventy (60%) were papillary, 36 (30%) were follicular, and 11 (10%) were Hürthle cell adenocarcinomas. The mean length of follow-up was 57.7 months. Adverse prognostic factors according to multivariate analysis were adjacent tissue infiltration (p = 0.0004), histologic type (p = 0.0049), and patient age (p = 0.033). The nuclear DNA content of tumor cells and of morphologically normal adjacent tissue was assessed by image cytometry, and correlations between nuclear DNA content and prognostic factors were examined. Fifty-four (75%) adenocarcinomas were classified as aneuploid, 9 (13%) as diploid, and 9 (12%) as borderline. Thirty-four (60%) specimens of morphologically normal adjacent tissue were classified as aneuploid, 18 (32%) as diploid, and 5 (8%) as borderline. The correlation between tumor ploidy and selected prognostic factors was statistically significant for patient age (p = 0.004) and histologic type (p = 0.033). Despite the fact that ploidy could not be identified as a prognostic factor, we suggest that, because of its correlation with age and histologic type, it might prove prognostic if the number of patients were increased. We also emphasize the importance of evaluating morphologically normal adjacent tissue because of the high rates of aneuploidy in these areas.     

Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia

BACKGROUND: Suprabasal expression of Ki-67 is assessed as a marker for oral dysplasia. The study involved non-neoplastic epithelium adjacent to 74 oral squamous cell carcinomas. METHODS: An immunohistochemical technique was carried out (peroxidase-antiperoxidase) with the monoclonal antibody MIB-1. Epithelial expression of Ki-67 was classified as being absent, basal, and suprabasal. The epithelium was normal in 19 cases, hyperplastic in 38 cases, and dysplastic in 37 cases. The dysplasia was slight in 20 cases, moderate in 12 cases, and severe in 5 cases. RESULTS: The results of the expression of Ki-67 were in normal epithelium, basal expression 9 cases, absent 10 cases; in hyperplastic epithelium, basal expression 18 cases, absent 20 cases; in dysplastic epithelium, basal and suprabasal expression (always jointly) 27 cases, absent 10 cases; all the severe and moderate dysplasia cases expressed suprabasal Ki-67. A significant association was observed between the presence (p <.0001) and severity (p <.007) of the dysplasia and the suprabasal expression of Ki-67.     

Analysis of both NM23-h1 and NM23-H2 expression identifies "at-risk" patients with colorectal cancer

Metastasis is the manifestation most directly affecting survival for patients with colorectal carcinoma. Identification of high-risk markers for metastases would allow focused selection of patients for adjuvant chemotherapy. Reports of the relationship between the putative metastasis suppressor NM23 and metastasis and/or survival in colorectal cancer patients are conflicting. The purpose of this study was to separately assess expression of NM23-H1 and NM23-H2 in primary colon cancers and determine whether expression was associated with regional nodal disease and/or liver metastases. Four patient cohorts were selected on the basis of histopathological staging at primary surgery (lymph node status/liver metastasis): -/- (n = 46), +/- (n = 47), -/+ (n = 43), and +/+ (n = 46). Primary tumors were evaluated by semiquantitative immunohistochemical analysis of NM23-H1 and NM23-H2. NM23-H2 expression was not related to survival; however, there was a modest survival advantage with low expression of NM23-H1 (P = 0.027). NM23-H1 expression in the +/+ group was increased compared with the other groups (P < 0.001). The -/+ group had the lowest expression of NM23-H2 (P < 0.001). This analysis distinguishes two high-risk groups of colorectal cancer patients. Prior discrepancies regarding the usefulness of NM23 staining may be explained by the need to evaluate both serotypes in addition to standard histopathological analysis to identify specific "at-risk" groups.