Nehal A. Radwan

The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1

BackgroundThe ability to distinguish hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) involving the liver and cholangiocarcinoma (CC) by immunohistochemistry has been limited by the lack of a reliable positive marker for hepatocellular differentiation. Arginase-1 is a marker for HCC recently described in some literature.AimTo examine the immunohistochemical staining of arginase-1 in cases of HCC, MC involving the liver and CC as compared to hepatocyte paraffin antigen -1 (HepPar-1) in an attempt to further define the diagnostic utility of arginase-1 in differentiating these tumors.Materials and methodsA comparative immunohistochemical study of arginase-1 and HepPar-1expression was performed in 50 HCC cases, 38 cases of MC to the liver from varying sites, 12 cases of CC and 10 specimens of normal liver tissues. The predictive capacity of arginase-1 and HepPar-1 staining was determined using sensitivity, specificity, positive predictive value, and negative predictive value calculations.ResultsAll normal liver tissues (no=10), non- neoplastic cirrhotic liver tissues adjacent to HCC (no=42) as well as those adjacent to MC (no= 9) showed diffuse and strong immunostaining for both arginase-1 and HepPar-1. Arginase-1 demonstrated positive immunoreactivity in 42 of 50 (84%) cases of HCC compared with 35 of 50 (70%) for HepPar-1. Only one of 38 (2.6%) cases of MC and one of 12 (8.3%) cases of CC showed positive immunoreactivity for arginase-1. In contrast, HepPar-1 immunoreactivity was detected in 6 of 38 (15.8%) cases of MC and in 2 of 12 (16.7%) cases of CC. Arginase -1 showed a significantly higher sensitivity for HCC diagnosis (84%) compared to HepPar -1(70%) (p=0.016). The specificity of arginase-1 for HCC diagnosis was higher (96%) than that of HepPar -1 (84%); nevertheless, this was not statistically significant (p=0.109). Howerver, the combination of both immunomarkers for the diagnosis of HCC, raised the specificity to 100%.ConclusionArginase-1 immunostaining has a higher sensitivity and specificity than HepPar-1 for HCC diagnosis. Furthermore, the combined use of arginase-1 and HepPar-1 can provide a potentially promising tool to improve the accuracy in distinguishing HCC from metastatic carcinoma and cholangiocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9991436558072434.

Perspectives on the immunologic microenvironment of astrocytomas.

Background The microenvironment of astrocytomas includes infiltrative inflammatory cells that are dynamic in nature, possibly reflecting tumor biology. We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a better understanding of their immunobiology. Methods Immunohistochemical expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21 anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas. The inflammatory infiltrate was classified based on microanatomic location as perivascular and intratumoral, and subsequently graded semiquantitatively. Results Perivascularly, CD68-positive infiltrate was noted in 71.4% of glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7% of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P = 0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was only associated with glioblastoma. A CD20-positive infiltrate was only detected in the perivascular space of a single case of diffuse astrocytoma. Conclusion These data indicate a distinct immune profile in the glioblastoma microenvironment primarily related to the prevalence of macrophages. Thus, novel glioblastoma therapies should address this key CD68-positive population and its possible role in generating an antitumor immune response.

Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt

Helal TEA, Khamis NS, El‐Sharkawy TM, Nada OH, Radwan NA. Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt. APMIS 2010; 118: 934–40.

Y-Type Urethral Duplication: A True Variant of the Anomaly or a Misnomer?

Objectives The objective of this study was to define anatomical and radiological features of the so-called Y-type urethral duplication. Methods The study included four male patients and one female patient with congenital connection between the urogenital tract and the external anal orifice. Investigations included renal sonography, urethrograms, and magnetic resonance imaging pelvis in the last patient. The urethrograms of male patients were carefully reviewed, in addition to available urethrograms of similar cases that could be obtained through searching the literature. Results Unlike cases of urethral duplication, the male patients had always a complete prepuce and a functioning anterior urethra in 25%. The accessory uroanal channel had almost always a constant origin from the posterior urethra. Some tension seems to be exerted by the urethroanal tract pulling on and causing a kink in the posterior urethra. Management was simple in patients without anterior urethral hypoplasia (one male and the female patient). Both were treated by simple excision of the communicating ano-urogenital tract through a perineal approach with an excellent outcome. Histopathological examination of excised tracts revealed stratified squamous cell in the former and transitional cell lining in the latter. In patients with hypoplastic anterior urethra, staged urethral reconstruction was performed in two, and progressive dilatation of hypoplastic anterior urethra was tried in the last patient. Conclusion Several observations would support diagnosing the congenital connection between the urinary tract and the external anal orifice in the male as a congenital fistula rather than an accessory urethra. Confirming and accepting this information may have its impact on changing the current surgical approach.

Role of alpha methylacyl-coenzyme A racemase in differentiating hepatocellular carcinoma from dysplastic and nondysplastic liver cell lesions

Distinction of hepatocellular carcinoma (HCC) from liver cell dysplasia (LCD) is one of the problems faced by pathologists. In spite of various methods claimed to differentiate between these 2 lesions, no reliable marker is available until now. The aim of the study was to assess the value of alpha methylacyl-coenzyme A (COA) racemase (AMACR) in distinguishing HCC from LCD. Formalin-fixed, paraffin-embedded tissue sections from 30 HCCs and 30 nonneoplastic liver tissues (12 dysplastic and 18 nondysplastic lesions) were immunostained for AMACR. Staining intensity was interpreted as low (negative, mild) and high expressions (moderate, marked). Alpha methylacyl-COA racemase showed high expression in 21 (70%) of 30 HCCs and 7 (58.3%) of 12 LCDs. All 18 nondysplastic lesions revealed low AMACR expression. The percentage of high AMACR expression was significantly more in HCC and LCD as compared with nondysplastic lesions (P = .001 in each). There was no significant difference in AMACR expression between HCC and LCD. Furthermore, the pattern of AMACR immunostaining was coarsely granular cytoplasmic positivity in HCC as well as LCD in comparison with the weak finely granular in nondysplastic lesions. Alpha methylacyl-COA racemase cannot discriminate HCC from LCD, although it can separate HCC and LCD from nondysplastic lesions.

Immunohistochemical expression of stem cell markers CD133 and Oct4 in colorectal adenocarcinoma

Introduction Colon cancer is a deadly disease affecting millions of people worldwide. The cancer stem cell (CSC) concept has been proposed as an attractive theory to explain cancer development and is considered as target for the development of diagnostics and therapeutics. Colon CSCs may drive carcinogenesis by their tumor initiation and maintenance capabilities, thus accounting for chemotherapeutic failure. Although many CSC markers have been proposed, there is neither complete agreement with regard to them, nor has their presence in the early phases of carcinogenesis been established. We evaluated the immunohistochemical expression of stem cell markers CD133 and Oct4 using the avidin–biotin immunoperoxidase technique to investigate their clinical importance in the initiation and progression of colorectal cancer. Results CD133 immunostaining was higher in nonmetastatic tumors, suggesting the loss of its character in advanced metastatic lesions. Oct4 was overexpressed in malignant tumor cells compared with normal colonic epithelium and was also expressed more in late Duke stages and metastatic tumors. In conclusion, we show that Oct4 may play a role in colorectal adenocarcinoma development and progression, and we suggest its utilization as a significant prognostic marker in colorectal carcinoma patients.

Relationship between hepatic progenitor cells and stellate cells in chronic hepatitis C genotype 4

Hepatitis C virus (HCV) infection represents a major health problem in many areas of the world, especially Egypt. Hepatic progenitor cells (HPCs) and hepatic stellate cells (HSCs) have been implicated in fibrosis progression in chronic HCV. The aim of this study was to investigate the role of HPCs and HSCs in chronic HCV infection and the relationship between both cell types. This retrospective study was conducted on 100 chronic HCV patients. Immunohistochemistry was performed on liver tissue sections for cytokeratin 19 (progenitor cell markers), smooth muscle actin (stellate cell markers), matrix metalloproteinase‐9 (MMP‐9), and transforming growth factor beta (TGF‐ß). The necroinflammatory activity was significantly related to the number of isolated HPCs and TGF‐ß expression (p = 0.003 and p = 0.001 respectively). Advanced stages of fibrosis showed significantly increase number of HPCs (p = 0.001), higher ratio of HSCs (p = 0.004), more expression of TGF‐ß (p = 0.001) and MMP‐9 (p = 0.001). There was a significant direct correlation between immunoexpression of HPCs and HSCs for isolated cells (r = 0.569, p = 0.001) and ductular reaction (r = 0.519, p = 0.001). Hepatic progenitor cells and stellate cells play a significant role in the development and progression of fibrosis in chronic HCV. More interestingly, the significant direct correlation between HPCs and HSCs suggests a synergistic interrelation.

Diagnostic value of the combined use of SATB2 and CDX2 in mucinous carcinoma of colorectal origin

Background Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical dilemma. The ability to confirm or exclude a diagnosis of carcinoma of colorectal origin by immunohistochemistry has been limited by the lack of a reliable positive marker for colorectal differentiation. Caudal type homeobox 2 (CDX2) has been reported to be expressed in intestinal adenocarcinomas; yet, it is also expressed in other tumors such as those of the pancreas, bile ducts, bladder, endometrium, and ovary. Special AT-rich sequence-binding protein 2 (SATB2) has been recently linked to colorectal cancer. The diagnostic role of SATB2 in mucinous carcinoma of colorectal origin has not been previously elaborated. Aim The aim of this study was to investigate the diagnostic value of SATB2 in differentiating mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins as compared with that of CDX2. Materials and methods A comparative immunohistochemical study of SATB2 and CDX2 expression was performed in 42 cases of primary mucinous carcinomas (colorectal=10, breast=14, cervix=10, stomach=8) and 22 cases of metastatic mucinous colorectal carcinoma. The predictive capacity of SATB2 and CDX2 expression for diagnosing the mucinous carcinoma of colorectal origin was determined individually and in combination using sensitivity, specificity, and positive and negative predictive value calculations. Results SATB2 demonstrated positive immunoreactivity in all cases of primary colorectal carcinoma and 81.8% of metastatic colorectal carcinomas in addition to 57.1% of breast, 40% of cervical, and 25% of gastric tumors. CDX2 was positively expressed in 60% of primary colorectal carcinomas and 72.7% of metasty tatic colorectal carcinomas, but it was negative in all noncolonic primary mucinous carcinomas. The SATB2 expression showed a sensitivity of 100% and a specificity of 56.2% in identifying colorectal origin of mucinous carcinomas, compared with 60 and 100% for CDX2 expression, respectively. The combined use of both SATB2 and CDX2 raised both the sensitivity and the negative predictive values to 100% if any of the two markers showed positivity as compared with the isolated use of CDX2. Conclusion SATB2 is a more sensitive yet less specific marker for diagnosis of mucinous carcinoma of colorectal origin as compared with CDX2. SATB2 in combination with CDX2 increases the accuracy of distinguishing mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins; therefore, SATB2 is considered a useful marker in this respect.