检测pT_(1-4a)N_(1-3)M_0期胃癌淋巴结微转移检测的临床意义

目的:探讨胃癌淋巴结微转移及临床病理因素对p T1-4aN1-3M0期胃癌患者术后5年无瘤生存率的影响。方法:选取我院2009年1月至12月期间胃肠外科单一手术组行D2胃癌根治术p T1-4aN1-3M0期患者63例1427枚HE染色阴性淋巴结,应用免疫组化法检测这些淋巴结中CK19表达,观察微转移的情况并分析发生微转移的胃癌患者临床病理特征及对患者5年无瘤生存率的影响。结果:临床病理分期p T1-4aN1-3M0胃癌患者中,经免疫组化染色,1427枚HE常规染色阴性淋巴结中CK19阳性表达率为15.49%(221/1427);63例胃癌患者中CK19表达阳性率39.68%(25/63);术后随访时间5.6~68.5月(平均时间43.88月),淋巴结中CK19阴性表达、阳性表达患者的总5年生存率分别为52.63%、28.00%;两者无瘤生存率差异有统计学意义(x2=8.677,P=0.003)。淋巴结CK19阳性表达与胃癌患者的肿瘤直径(P0.05)、浸润胃壁深度(P0.05)有关。COX生存回归分析显示淋巴结微转移为独立预后因素。25例患者发现淋巴结微转移并推荐再分期,再分期率39.68%(25/63)。结论:p T1-4aN1-3M0期胃癌病人,CK-19免疫组化法染色能检出常规HE染色阴性淋巴结中的微转移,有助于细化分期、判断预后及指导治疗。     

CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection

This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor–node–metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan–Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19−/GPC3+ and CK19−/GPC3− three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19−/GPC3+ HCC, then CK19−/GPC3−HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients.     

SM047 immunoreactivity in peritoneal fluids

SM047 is a recently developed monoclonal antibody generated against an ovarian adenocarcinoma cell line. A recent immunohistochemical study has shown that SM047 is strongly expressed in tissue sections of most ovarian serous adenocarcinomas. This study aimed to ascertain whether SM047 staining is of value in cytological preparations of peritoneal fluid. A total of 206 consecutive peritoneal fluids were stained immunocytochemically with SM047, CA125, monoclonal carcinoembryonic antigen (mCEA), Ber-EP4 and cytokeratins (CK7 and 20). SM047 positivity was present in reactive mesothelial cells in 117 of 141 (83%) benign cases in which these were present. SM047 positive tumour cells were present in 22 of 23 (96%) ovarian serous adenocarcinomas and in small numbers of gastric adenocarcinomas (two of three), mesotheliomas (one of two) and pancreatic adenocarcinomas (one of one). All six colorectal and two breast adenocarcinomas were negative with SM047. Reactive mesothelial cells in all cases were positive with CK7 and in most cases with CA125. They were negative with CEA, Ber-EP4 and CK20. All adenocarcinomas were positive with Ber-EP4 and mesothelial cells were always negative. All colorectal adenocarcinomas were positive with CK20. This study shows that SM047 staining may be of value in the diagnosis of an ovarian serous adenocarcinoma in peritoneal fluids. Negative staining helps to exclude a primary ovarian serous adenocarcinoma and is characteristic of colorectal adenocarcinoma. The small numbers of other malignancies in the study precludes a judgement of the value of SM047 staining in these neoplasms. SM047 staining may be useful, as part of a larger panel, in the work up of patients with peritoneal effusions.     

Expression of cytokeratin 19 and matrix metalloproteinase 2 predicts lymph node metastasis in hepatocellular carcinoma

The purpose of this study was to assess the value of cytokeratin 19 (CK19) and matrix metalloproteinase 2 (MMP-2) in predicting lymph node metastasis (LNM) and survival after curative resection in hepatocellular carcinoma (HCC) patients. Expression of CK19 and MMP-2 in tumor tissue was assessed through immunohistochemical staining of tissue microarrays (TMAs), which were constructed using samples from HCC patients with (n = 123) and without (n = 145) LNM. Positive CK19 expression was correlated with LNM (P < 0.001), satellite lesions (P = 0.016), and lymph node location (P = 0.039). High MMP-2 expression correlated with LNM (P < 0.001), UICC T stage (P = 0.023), and Edmondson grade (P = 0.022). Moreover, CK19 expression correlated with MMP-2 expression (P = 0.033). CK19 and MMP-2 expression were predictive of HCC LNM (AUC: 0.640; 95% CI: 0.572–0.707; P < 0.001 and AUC: 0.611; 95% CI: 0.544–0.679; P = 0.002, respectively). CK19 and MMP-2 expression were independent prognostic factors for disease-free survival (P = 0.031 and P = 0.012, respectively) and overall survival (P = 0.013 and P = 0.018, respectively) in HCC patients with LNM. CK19 expression (P < 0.001), MMP-2 expression (P = 0.006), and UICC T stage (P < 0.001) were independent risk factors for developing LNM in HCC. These findings show that CK19 and MMP-2 expression may be beneficial in predicting HCC LNM and survival.     

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

The function of creatinekinase (CK) and its effect on phosphorus metabolites was studied inlivers of transgenic mice expressing human ubiquitous mitochondrial CK(CK-Mit) and rat brain CK (CK-B) isoenzymes and their combination.³¹P NMR spectroscopy and saturation transfer were recordedin livers of anesthetized mice to measure high-energy phosphates andhepatic CK activity. CK reaction velocity was related to total enzyme activity irrespective of the isoenzyme expressed, and it increased with increasing concentrations of creatine (Cr). The fluxesmediated by both isoenzymes in both directions (phosphocreatine or ATP synthesis) were equal. Over a 20-fold increase in CK-Mit activity (28-560 µmol · g wetwt¹ · min¹), the fraction ofphosphorylated Cr increased 1.6-fold. Hepatic free ADP concentrationscalculated by assuming equilibrium of the CK-catalyzed reaction in vivodecreased from 84 ± 9 to 38 ± 4 nmol/g wet wt. Calculatedfree ADP levels in mice expressing high levels of CK-B (920-1,635µmol · g wet wt¹ · min¹)were 52 ± 6 nmol/g wet wt. Mice expressing both isoenzymes had calculated free ADP levels of 36 ± 4 nmol/g wet wt. Thesefindings indicate that CK-Mit catalyzes its reaction equally well inboth directions and can lower hepatic apparent free ADP concentrations.

     

The spectrum of cytokeratins expressed in the adult human cornea, limbus and perilimbal conjunctiva

The aim of this study was to detect a spectrum of cytokeratins (CK) present in the adult human cornea, limbus and perilimbal conjunctiva. Cryosections from seven corneo-scleral discs were fixed, and indirect immunofluorescent staining was performed using antibodies directed against CK1-CK10 and CK13-CK20. The percentage of positive cells was calculated in the epithelium of the cornea, limbus and perilimbal conjunctiva. Quantitative real time RT-PCR (qRT-PCR) was used to detect CK6 and CK18 expression in the corneal and conjunctival epithelium. The most intense staining present throughout the cornea was observed for CK3, CK5 and CK14; CK19 was found at the corneal periphery only. CK4 and CK10/13 revealed mild to moderate positivity mostly in the superficial layers of the cornea. The suprabasal cell layers of all examined areas showed a strong positivity for CK16. A heterogeneous staining pattern with a centrifugal decrease in the signal was observed for CK8 and CK18. CK5/6, CK14 and CK19 were present in the limbus, where a positive signal for CK3 was observed in the suprabasal and superficial cells only. In contrast to the cornea, CK15 appeared in the basal and suprabasal layers of the limbus. The perilimbal conjunctiva showed strong immunostaining for CK10/13, CK14 and CK19. A moderate signal for CK7 was detected in the superficial layers of the conjunctiva. qRT-PCR confirmed CK6 and CK18 expression in the corneal and conjunctival epithelium. The detailed characterization of the corneal, limbal and perilimbal conjunctival epithelium under normal circumstances may be useful for characterizing the changes occurring under pathological conditions.     

Expression of cytokeratin 19 and protein p63 in fine needle aspiration biopsy of papillary thyroid carcinoma

OBJECTIVE: To analyze the immunocytochemical distribution of CK19 and p63 on archival cytologic smears of 27 papillary thyroid carcinomas (PTCs), 22 benign thyroid lesions and 5 malignant non-PTC lesions. STUDY DESIGN: Archival cytologic smears of 27 papillary carcinomas, 22 benign thyroid lesions and 5 malignant nonpapillary carcinomas were processed for immunocytochemical detection of CK19 and p63, and results were compared. RESULTS: CK19 showed strong cytoplasmic staining in 22/27 fine needle aspiration biopsies (FNABs) of PTCs, in 5 benign lesions and in 4 malignant lesions of the control group. p63 Positivity was present in FNABs of 20/27 PTC and in 1 FNAB of nodular hyperplasia. Eighteen FNABs of PTC (66.6%) showed both strong CK19 staining and p63-positive cells, whereas none of the control cases showed coexpression of CK19 and p63. CONCLUSION: Coexistence of strong CK19 positivity and p63-positive cells can enhance the cytologic diagnosis of PTC.     

Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2

A series of novel iodinated benzimidazoles have been prepared by iodination of respective benzimidazole with iodine and periodic acid in sulfuric acid solution. Additionally several 2-substituted- and N-1-carboxymethyl-substituted derivatives of 4,5,6,7-tetraiodobenzimidazole (TIBI) were obtained. For sake of comparison, some new 4,5,6,7-tetrabromobenzimidazoles were also synthesized. The ability of the new compounds to inhibit protein kinase CK2 has been evaluated. The results show that 4,5,6,7-tetraiodobenzimidazoles are more powerful inhibitors of CK2 than their tetrabrominated analogs. Molecular modeling supports the experimental data showing that tetraiodobenzimidazole moiety fills better the binding pocket than respective tetrabromo and tetrachlorocompounds. To note that 4,5,6,7-tetraiodobenzimidazole (TIBI) is one of the most efficient CK2 inhibitors (K_i = 23 nM) described to date.     

Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction

It is currently unclear whether intestinal metaplasia at the esophagogastric junction and in the distal esophagus represent a continuum of the same underlying disease process, i.e., gastroesophageal reflux, or constitute different entities with a different pathogenesis. Biopsies below the Z line might show specialized epithelium in some patients and the question is whether this is another form of short segment Barrett's esophagus or whether it is related to a generalized atrophic process of the stomach. Data from recent studies regarding the expression of cytokeratin CK7 and CK20 in intestinal metaplasia (IM) found at the gastroesophageal junction are conflicting. Prompted by these data we undertook the present study: a) to evaluate the expression of CK7 and CK20 in IM of the gastric cardia and to compare the findings with those in patients with Barrett's esophagus and IM of the gastric corpus and antrum mucosa; and b) to evaluate the immunophenotype of non-intestinalized cardiac mucosa and to compare it with that of normal gastric epithelium. We studied the expression of CK7 and CK20 on biopsy specimens from patients with long-segment Barrett's esophagus (n=17) and surgical resection and biopsy specimens of gastric cardia (n=15), corpus (n=14) and antrum (n=22) from patients with histological evidence of IM. Eighty-four biopsy specimens from 42 patients (antrum n=15, corpus n=20, cardia n=7) without evidence of IM were studied as a control group. We observed an immunophenotype characterised by diffuse moderate to strong CK7 staining on the surface and crypt epithelium combined with strong CK20 staining on the surface and superficial part of the crypts in 94.1% (16/17) of the cases with long-segment Barrett's esophagus, but in none of the 36 cases with IM in distal stomach (antrum and corpus). IM in the gastric cardia expressed the immunophenotype seen in IM of the gastric mucosa in 93.3% (14/15) of the cases. On the other hand, normal cardiac epithelium expressed patchy strong CK7 staining on the surface epithelium and on both, superficial and deep parts of the pits combined with patchy strong CK20 staining on the surface epithelium and superficial pits, a feature permitting distinction of the normal cardiac epithelium from those of the normal gastric antrum and corpus epithelium. We conclude that the expression of cytokeratins 7 and 20 can be used to distinguish the origin of IM of the gastroesophageal junction. The CK7/20 immunophenotype of IM in the gastric cardia closely resembles that of the IM in the gastric antrum and corpus and is different from IM in long-segment Barrett's esophagus. In contrast, the CK7/20 immunophenotype of the cardiac epithelium is different from that of the gastric antrum and corpus mucosa, suggesting that cardiac epithelium might not be a native normal gastric epithelium but one that is acquired as a consequence of longstanding inflammation. Changing pattern of CK7 and CK20 expression from normal to intestinalized epithelium suggests that IM arising from cardiac epithelium might have distinctive features.     

PTEN、p57／Kip2和CK19在非小细胞肺癌中的表达及意义研究

探讨非小细胞肺癌中PTEN、p57/Kip2和CK19的表达情况和临床意义。选取58例非小细胞肺癌手术切除标本,采用SP法进行免疫组织化学染色。PTEN、p57/Kip2和CK19的阳性表达率分别为44.8%、56.9%和98.3%。PTEN和p57/Kip2在低分化肿瘤中表达显著降低或缺失,在腺癌中的表达强度高于鳞癌;CK19几乎在所有的肺癌组织中均表达,且在腺癌中的表达强度高于鳞癌。PTEN和p57/Kip2的低表达参与肿瘤的生长分化和进展,并提示预后不良。     

Isolation,culture, and verification of human sweat gland epithelial cells

Human sweat gland epithelial cells (SGECs) have been isolated and grown in vitro, However, slow proliferation makes the culture of these cells extremely difficult. The present study was carried out to explore the modified culture medium for SGECs in vitro. Full-thickness skin samples were minced (1 mm³) and digested overnight with type II collagenase. The gland coils were removed under an inverted phase-contrast microscope. An adherent culture method was used to isolate and culture SGECs. Staining with hematoxylin and eosin was performed, followed by observation of the morphologic features of these cells. Immunofluorescence staining with antibodies to cytokeratins CK7, CK18, and CK19 and carcinoembryonic antigen (CEA) was performed to verify the presence of SGECs. Growth curves by MTT were created for cells grown in serum-free keratinocyte medium and in modified keratinocyte medium containing 2.5% fetal bovine serum (FBS). One week after culturing, the cells grew well and were polygonal or irregular in shape by inverted phase contrast microscopy. Cell fusion, with a characteristic paving-stone arrangement, reached 100% after approximately 3 weeks in culture. Immunofluorescence staining indicated expression of CK7, CK18, CK19, and CEA. Compared with SGECs grown in serum-free keratinocyte medium, the proliferation of SGECs grown in modified culture medium with low concentration of FBS at days 6, 9, and 12 was significantly accelerated (p < 0.05). This study suggests that keratinocyte medium supplemented with 2.5% FBS is effective and suitable for the culture of SGECs.     

The Normal Transverse Mesocolon and Involvement of the Mesocolon in Acute Pancreatitis: An MRI Study

Objective

To study the MRI findings of the normal transverse mesocolon and the involvement of the mesocolon in acute pancreatitis (AP) as well as the relationship between the involvement of the mesocolon and the severity of AP.

Materials and Methods

Forty patients without pancreatic disorders were retrospectively analyzed to observe the normal transverse mesocolon using MRI; 210 patients with AP confirmed by clinical and laboratory tests were retrospectively analyzed using MRI to observe transverse-mesocolon involvement (TMI). The severity of TMI was recorded as zero points (no abnormalities and transverse-mesocolon vessel involvement), one point (linear and patchy signal in the transverse mesocolon) or two points (transverse-mesocolon effusion). The AP severity was graded by the MRI severity index (MRSI) and the Acute Physiology And Chronic Healthy Evaluation II (APACHE II) scoring system. The correlations of TMI with MRSI and APACHE-II were analyzed.

Results

In a normal transverse mesocolon, the display rates of the middle colic artery, the middle colic vein and the gastrocolic trunk on MRI were 95.0%, 82.5% and 100.0%, respectively. Of the 210 patients with AP, 130 patients (61.9%) had TMI. According to the TMI grading, 40%, 39% and 20% of the patients were graded at zero, one and two points, respectively. TMI was strongly correlated with the MRSI score (r = 0.759, P = 0.000) and the APACHE-II score (r = 0.384, P = 0.000).

Conclusion

MRI could be used to visualize transverse-mesocolon involvement. The severity of TMI could reflect that of AP in the clinical setting and imaging. TMI might be a supplementary indicator of the severity of AP.     

Flow cytometric analysis of DNA content and keratins by using CK7, CK8, CK18, CK19, and KL1 monoclonal antibodies in benign and malignant human breast tumors.

We have used a double-labelling flow cytometry analysis of keratin (CK) and DNA in breast cancer. Five monoclonal anti-keratin antibodies were tested: KL1 recognizing Mr 55,000-57,000 keratins, and "anti-glandular epithelia," LE41, RGE-53, and LP2K specific for CK n. 7, 8, 18, and 19 of Moll's classification, respectively. Flow cytometric (DNA-CK) analysis was performed on 10 benign and 19 malignant human breast tumors. All the benign tumors were diploid and 63% of the malignant tumors were aneuploid. This technique permits the analysis of DNA in the epithelial fraction alone. In aneuploid tumors, gating the DNA-keratin-positive population allowed accurate DNA analysis without interference due to debris background and non-epithelial cells. Moreover, double-labelling using the CK19 antibody gave a better identification of near-diploid tumors. An enhancement of keratin expression in malignant tumors was observed with CK 19 (P less than 0.001), KL1 (P less than 0.01), CK 8 (P less than 0.05), and CK18 (n.s.) compared to benign tumors. The comparison of keratin expression in aneuploid and diploid malignant tumors revealed reduced CK8, CK18, and CK19 in the former.     

Serrated Pathway Adenocarcinomas: Molecular and Immunohistochemical Insights into Their Recognition

Introduction

Colorectal adenocarcinomas (CRC) developed through serrated pathway seem to present particular behavior compared with the non-serrated ones, but recognition of them is difficult to do. The aim of our paper was to establish some criteria to facilitate their identification.

Materials and Methods

In 170 consecutive CRCs, we performed immunohistochemical staining with Cytokeratin 7 (CK7) and Cytokeratin 20 (CK20) and also with p53 and MLH-1. At the same time, we analyzed BRAF and K-ras mutations and the microsatellite status of CRC.

Results

26.47% of cases expressed CK7, and 16.47% were CK20-negative. Diffuse positivity for CK7 was associated in the proximal colon with CK20 negativity or weak positivity, BRAF mutations, lack of K-ras mutations, and p53 and MLH-1 negativity. All these cases were microsatellite-unstable and were diagnosed in stage II. Those cases from the distal colon and rectum that expressed CK7 were K-ras-mutated and had low p53 index and MLH-1 positivity, independent of the CK20 expression.

Conclusions

CK7, associated with MLH-1 and p53 expression, and also with the microsatellite status, BRAF and K-ras pattern, might be used to identify the CRC potentially going through serrated pathway. The serrated pathway adenocarcinomas of the proximal colon that do not display the morphological features of this pattern are more frequent CK7+/p53−/MLH-1−/BRAF-mutated/K-ras-wt/MSI cases, but those located in the distal colorectal segments seem to be CK7+/CK20+/p53−/MLH-1+/BRAF wt/K-ras-mutated/MSS cases.     

Cytokeratin 20 immunoreactivity in renal oncocytomas.

Cytokeratins (CKs) are a group of 20 antigenically distinct intermediate filaments, generally confined to epithelia and their neoplasms. Immunostaining for CKs, in particular coordinate staining for CK7 and CK20, has become a useful tool in diagnostic pathology. Although studies defining CK distribution in neoplasms identify 0--7.7% of renal cell carcinomas (RCCs) positive for CK20, none has described the incidence of CK20 immunopositivity in renal oncocytomas (ROs). Distinction between RCC and RO may be difficult but this distinction is clinically significant, prompting us to establish the incidence of CK20 positivity in RO. We selected fifteen surgical cases of RO from our archives and studied their immunoreactivity for CKs including CK7 and CK20; 12/15 (80%) were positive for CK20, with variation in the number of cells staining. There was also variation in the distribution of CKs within the cells, including diffuse cytoplasmic, perinuclear, and a punctate or dot-like pattern. Such punctate staining corresponds to cytoplasmic balls of intermediate filaments and has been described with CAM 5.2 in RO and CK20 in Merkel cell carcinomas. Our findings suggest that CK20 immunohistochemistry is a useful tool for distinguishing RCCs from ROs. (J Histochem Cytochem 49:919-920, 2001)     

Macro CK type 1 as a major component of serum creatine kinase activity in pregnant sheep

Electrophoretic separation of creatine kinase (ATP: creatine phosphotransferase, E.C. 2.7.3.2) isoenzymes in agarose gel was made in the serum of 93 sheep of three Slovenian domestic breeds (Solcavska, Pramenka and Bovska breeds). 44 sheep were pregnant between 112 and 135 days at the time of the blood collection. The median value of serum total CK activity for all animals investigated was 82 U/l. After direct immunoinhibition of CK with anti-M-CK monoclonal antibodies the total CK activity remained the same (88 U/l, P = 0.354). There were significant differences among breeds in CK activity for the Solcavska (101 U/l), Bovska (89 U/l) and Pramenka breeds (73 U/l), respectively (Kruskal–Wallis one way analysis of variance, P < 0.01), and between pregnant (105 U/l) and non-pregnant animals (76 U/l), irrespective of the breed (Mann–Whitney rank sum test, P < 0.05). According to electrophoresis, all non-pregnant sheep had exclusively free CK-BB serum bands activity. In all pregnant sheep coupled dimeric BB variant appeared as macro-CK type 1 in the range between 80% and 100% of total CK activity. The present study confirms the existence of an elimination mechanism for CK from the plasma abundance free CK-BB enzyme.     

Cytokeratin 20-positive hepatocellular carcinoma

The differential diagnosis between hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and metastatic colorectal adenocarcinoma (MCA) may be difficult when only based on morphology. For this purpose immunohistochemical analyses are often required, utilizing antibodies directed against CK8-18, Hep-Par1, glypican 3, CK7, CK19, CK20. Here we report a case of a 65-year-old man who presented with a clinical picture of decompensated cirrhosis. Ultrasonography revealed two nodular areas in the right liver lobe. Liver needle biopsy revealed micro-macronodular cirrhosis associated with HCC with trabecular and pseudoglandular patterns. Immunohistochemically, tumour cells were diffusely positive for CK8-18 and also diffusely immunostained by glypican 3 and Hep-Par1. Interestingly, a diffuse and strong staining for CK20 was detected in the vast majority of tumor cells, particularly in the areas showing a pseudo-glandular pattern. No immunostaining for CK7 and CK19 was found in the tumor cells. The tumor behaved aggressively, with a rapid diffusion to the whole liver. The patient died from the disease few months after presentation. These findings underline that the interpretation of the expression of CK20 alone in the differential diagnosis among HCC, CC and MCA should be done with caution because a diffuse immunoreactivity for CK20 alone may not rule out the diagnosis of HCC.Key words: hepatocellular carcinoma, cholangiocarcinoma, metastatic colorectal carcinomas, CK20.The differential diagnosis between hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and metastatic colorectal adenocarcinoma (MCA) may be difficult when only based on morphology (Terracciano et al., 2003).In fact, a subset of extrahepatic adenocarcinomas of different origin may show a solid “hepatoid” pattern virtually indistinguishable from HCC (Porcell et al., 2000). On the other hand, the undifferentiated form of HCC may mimic poorly differentiated tumors of different origin, while its tubular and adenoid variants may be indistinguishable from CC or from MCA.In these cases, immunohistochemical analyses are often required (Stroescu et al., 2006).The panel of antibodies utilized to solve this differential diagnosis includes: CK8-18 (Porcell et al., 2000) Hep-Par1 (Leong et al., 1998) (Zimmerman et al., 2001), glypican 3 (GPC3) (Yamauchi et al., 2005) (Capurro et al., 2003), CK7 (Maeda et al., 1996) (Chu et al., 2000), CK20 (Faa G et al., 1998), CK19, CEA and Alpha-fetoprotein (Onofre et al., 2007) (Lau et al., 2002).Immunoreactivity of tumour cells for CK8-18, Hep-Par 1 and GPC3 is considered suggestive of HCC; a diffuse immunoreactivity for CK7 and CK19 is in favour of the diagnosis of CC; a diffuse positivity for CK20 and negativity for CK7 are normally associated with MCA.Here we report a case of HCC with a peculiar immunohistochemical profile, characterized by the association of the typical immunoreactivity of HCC with a diffuse and strong positivity for CK20, generally considered typical of MCA.