Hayam A. Aiad

Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes

Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein–coupled receptor‐30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin‐fixed paraffin‐embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph‐vascular invasion (LVI) (p = 0.002), peri‐nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.

pS2 (TFF1) expression in prostate carcinoma: correlation with steroid receptor status.

pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen‐regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis.

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma

John Cunningham virus (JCV) encodes an oncogenic T‐antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.

Computerized nuclear morphometry in the diagnosis of thyroid lesions with predominant follicular pattern.

Background: Differential diagnosis of thyroid lesions with predominantly follicular pattern is one of the most common problems in thyroid pathology. Development of more objective and reproducible tools for diagnosis is needed. This work is aimed at studying the role of nuclear morphometry in differential diagnosis of different thyroid lesions having predominant follicular pattern. Material and methods: Semiautomatic image analysis system was used to measure a total of 8 nuclear parameters in 48 thyroid lesions including seven nodular goiter (NG), 14 follicular adenoma (FA), 14 follicular carcinoma (FC) and 13 follicular variant papillary carcinoma (FVPC). Results: The parameters related to nuclear size (area, perimeter, MaxD, MinD, nuclear size) and shape (L/S ratio, Form_AR) were significantly higher in neoplastic group (FA, FC, FVPC) when compared to non-neoplastic group (NG) P<0.05. The perimeter was the most reliable parameter (area under the cure (AUC)=97%) followed by area, MaxD, and size (all have AUC= 96%) then form-AR (90%), LS ratio (86%) and the least reliable was Min D (79%). Within the neoplastic group, most parameters related to size and shape of the nuclei was significantly higher in FVPC than in FA and FC (p ≤ 0.05). Nuclear area and size (AUC 77%) were the most reliable parameters for differentiation between FVPC and FA. The best cut off values for diagnosing FVPC are nuclear area ≥39.9μm2 and nuclear size ≥27.7μm2. However, there was no quantitative difference between FC and FA. Conclusion: Nuclear morphometric parameters may help in the differentiation between neoplastic and non-neoplastic thyroid lesions and between FVPC and follicular neoplasms (FC and FA) but they have no value in the differentiation between FC and FA.

Immunohistochemical expression of topoisomerase II a and tissue inhibitor of metalloproteinases 1 in locally advanced breast carcinoma

Objectives To evaluate immunohistochemical expression of topoisomerase II a (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in an attempt to identify their prognostic roles in locally advanced breast cancer (LABC). Background LABC is a heterogeneous clinical entity that remains a clinical challenge. Efforts are still needed to identify new markers in an attempt to predict response to therapy and prognosis. Patients and methods This study included 84 pretreatment needle core biopsies of LABC cases subjected to TOP2α and TIMP-1 immunohistochemical staining and the expression was correlated with some prognostic clinicopathlogical parameters of the patients studied. Results Fifty-seven of 84 cases (67.9%) showed positive TOP2 expression, with the proportion of TOP2α immunopositive cells (%score) ranging from 0 to 95%, mean ± SD of 27.84 ± 26.16%, and the median was 25%. Positive TOP2α expression was significantly associated with the presence of necrosis ( P = 0.03). There was also a near-significant association between positive TOP2α expression and high mitotic count ( P = 0.08). Forty-eight of 84 cases (57.1%) showed positive TIMP-1 expression with proportion of TIMP-1 immunopositive cells (%score) ranged from 0 to 95%, mean ± SD of 35.59 ± 32.93%, and the median was 30%. Positive TIMP-1 expression was significantly associated with a low apoptotic count ( P = 0.03). Conclusion TOP2α-positive expression in diagnostic samples of LABC patients is associated with poor prognostic features such as the presence of necrosis, whereas TIMP-1 is associated with a low apoptotic count.

The role of CK7, Ki-67, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates.

Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki‐67, cd34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in egyptian cholestatic neonates. APMIS 2012; 120: 529–38.

Diagnostic Role of p63 Immunostaining in Fine Needle Aspiration Cytology of Different Breast Lesions

Objective: To evaluate the potential diagnostic role of the myoepithelial marker p63 in fine needle aspiration cytology (FNAC) of breast in comparison to other diagnostic tools. Study Design: A total of 49 FNAC of breast were assessed according to clinical, mammographic, cytological findings, and p63 immunostaining on FNAC. The strength of agreement with final histological diagnosis (FHD) was measured by kappa test. Results: p63 was positive in myoepithelial cells of 75% (9/12) of benign cases and negative in 89% (33/37) of the malignant cases with strong agreement with the FHD (p < 0.0001, ĸ = 0.63). All the malignant positive cases showed variable degrees of in situ component. Only one malignant case (1/37, 0.03%) showed few p63 positive neoplastic cells in FNAC. Combined FNAC and p63 staining (with <25% cutoff point) to diagnose malignancy showed 100% sensitivity, 75% specificity, 92% positive predictive value, 100% negative predictive value, and 94% diagnostic accuracy. Most of the cytologically suspicious cases (7/9, 78%) showed negative p63 staining results, and all these suspicious cases (100%) proved to be malignant by the FHD. There was poor agreement between diagnosis according to positive background naked nuclei (NN) and the FHD (ĸ = 0.24 and p < 0.0001); however, presence of more than 74% positive NN is strongly suggestive of fibroadenoma. Conclusion: p63 immunostaining with a cutoff value of <25% to diagnose malignancy is a highly sensitive and specific myoepithelial marker which is recommended as an adjuvant tool to FNAC of breast in suspicious cases.

Fine Needle Aspiration Cytology of Chondroid Tenosynovial Giant Cell Tumor of the Hand.

Giant cell tumor (GCT) of tendon sheath is a localized form of tenosynovial GCT, which preferentially affects the joints of hands and feet. Chondroid metaplasia is a rare phenomenon in tenosynovial GCT either in localized or diffuse types. The current case investigates the cytological and histopathological features of chondroid GCT of tendon sheath in a 22-year-old female presenting with wrist swelling.

Hepatocellular carcinoma in Egypt: epidemiological and histopathological properties

Objectives To study the epidemiological and pathological properties of hepatocellular carcinoma (HCC) cases eligible for surgical resection. Background HCC is the sixth most common cancer worldwide and the third most common cause of cancer death. In Egypt, liver cancer forms 1.68% of the total malignancies. HCC constitutes 70.48% of all liver tumors among Egyptians. HCC represents the main complication of cirrhosis. Materials and methods This longitudinal study included 92 HCC patients who had undergone surgical intervention. Clinical and demographic data were collected from medical records, and paraffin blocks were retrieved from the Archives of the Pathology Department, National Liver Institute, Menoufia University, during the period between March 2007 and October 2014. Results revealed that 51.1% of the studied HCC patients were at least 58 years old, 81.5% male and 18.5% female, 51.2% of the patients had an a-fetoprotein level of at least 200 ng/ml and 95.7% were positive for hepatitis viral infection. Revision of the pathological data revealed that 82.6% of the HCC cases presented as a single focal lesion with a median size of 5 cm. About 76.1% were on top of a cirrhotic liver and 44.5% showed dysplastic changes and 96.7% of the cases were of the classic type. About 57.6% of the cases presented with stage T1 and 34.8% of the cases had lymphovascular invasion. Conclusion On the basis of 92 surgical specimens of HCC, most of the HCC in Egypt occurred in men who developed a cirrhotic liver due to HCV infection. Epidemiological and histopathological data of HCC highlight the importance of an integrated strategy for the prevention and the treatment of viral hepatitis infections and chronic liver disease.

The prognostic and predictive significance of PARP-1 in locally advanced breast cancer of Egyptian patients receiving neoadjuvant chemotherapy.

Purpose:PARP-1 is a chromatin-associated enzyme that has a role in DNA repair and cell death. PARP-1 inhibitors are suggested therapy specifically for BRCA deficient breast carcinoma; however, their efficacy in sporadic breast cancer is under investigations. This study aimed to evaluate the PARP-1 in locally advanced breast cancer (LABC) cases to determine its predictive significance for outcome and response to neoadjuvant chemotherapy (NCT). Materials and Methods:This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of nuclear PARP-1 (nPARP-1) and cytoplasmic PARP-1 (cPARP-1) was evaluated in pretreatment needle core biopsies (NCBs). Results were correlated with clinicopathologic features, overall survival (OS), disease-free survival (DFS), and response to NCT in postoperative specimens. Results:High nPARP-1expression was observed in 64/84 (76%) of cases and was significantly associated with a lower lymph node stage (P=0.04). High cPARP-1 was observed in 40/84 (48%) of cases and it was significantly associated with lower lymph node stage (P=0.022) and lower tumor grade (P=0.050). High nPARP-1 expression was significantly associated with high cPARP-1 expression (P=0.005). Low cPARP-1 expression was associated with no response to chemotherapy in tumor site (P=0.021). According to the univariate survival analysis, high nPARP-1 and high cPARP-1 were significantly associated to longer OS (P=0.017 and P=0.019, respectively). High nPARP-1 but not cPARP-1 showed trend toward improved OS in multivariate Cox-regression analysis (P=0.053). Conclusion:PARP-1 immunohistochemical expression is a marker of good prognosis and is predictive of response to NCT in LABC.