STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AAC) are lethal malignancies with modest benefits from surgery. SOX2 and STIM1 have been linked to anticancer activity in several human malignancies. This study included 94 tumor cases: 48 primary PDAC, 25 metastatic PDAC, and 21 primary AAC with corresponding non-tumor tissue. All cases were immunohistochemically stained for STIM1 and SOX2 and results were correlated with clinicopathologic data, patient survival, and BCL2 immunostaining results. Results revealed that STIM1 and SOX2 epithelial/stromal expressions were significantly higher in PDAC and AAC in comparison to the control groups. STIM1 and SOX2 expressions were positively correlated in the primary and metastatic PDAC (P = 0.016 and, P = 0.001, respectively). However, their expressions were not significantly associated with BCL2 expression. SOX2 epithelial/stromal expressions were positively correlated with the large tumor size in the primary AAC group (P = 0.052, P = 0.044, respectively). STIM1 stromal and SOX2 epithelial over-expressions had a bad prognostic impact on the overall survival of AAC (P = 0.002 and P = 0.001, respectively). Therefore, STIM1 and SOX2 co-expression in tumor cells and intra-tumoral stroma could contribute to the development of PDAC and AAC. STIM1/SOX2 expression is linked to a bad prognosis in AAC.

Is overexpression of CD163 and CD47 in tumour cells of breast carcinoma implicated in the recruitment of tumour-associated macrophages (TAMs) in tumour microenvironment? immunohistochemical prognostic study.

BACKGROUND: Now, targeted therapy and immunotherapy are promoted. tumour -Associated Macrophages (TAMs) are an essential component of immune-response in breast cancer(BC) with prognostic controversy. Additionally, their recruiting factors are still obscure. Purpose:This study aimed to evaluate the prognostic significance of CD163 and CD47 in BC of No Special Type (BC-NST) and to explore their suggested role in recruiting TAMs. MATERIAL AND METHODS: This immunohistochemical study was conducted on 91 archival specimens of breast cases. Immunoreactivity scores were correlated with TAMs density, clinicopathological data, and survival. RESULTS: Revealed the highest CD163 expression was detected in the pure DCIS group (p = 0.016), while the highest CD47 expression and high TAMs density were reported in the invasive group (p = 0.008, and p = 0.002 respectively) followed by the DCIS group. In IC-NSTs the CD163 and CD47 scores were associated with poor prognostic parameters like(high grade, advanced stage, distant metastasis, ER negativity,Ki67 index, post-surgical chemotherapy, poor NPI group, high mitotic count, dense infiltration of TAMs, shorter OS). Also, CD47 was associated with the dens infiltration of TAMs in DCIS (p = 0.001). There was a significant correlation between tumour cell expression of CD163 and CD47 in IC-NSTs and DCIS (p = 0.002 and p = 0.009 respectively). CONCLUSIONS: High CD163 and CD47 expressions in both DCIS andIBC are intimately associated, significantly associated with poor prognosis and are important provoking factors of TAMs.

Evaluation of the diagnostic utility of NCOA3, Maspin and VHL protein expression in pancreatic ductal adenocarcinoma: An immunohistochemical study.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal tumor with a high mortality rate. The distinction between PDAC and chronic pancreatitis is sometimes challenging on routine histopathological examination, highlighting the need to identify biomarkers that can facilitate this distinction. This retrospective study was conducted to evaluate the diagnostic utility of nuclear receptor co-activator 3 (NCOA3), Maspin and Von Hippel-Lindau protein (VHL) immunostaining in PDAC. Eighty cases of PDAC, 46 cases of chronic pancreatitis and 53 normal pancreatic tissue were immunohistochemically assessed using NCOA3, Maspin and VHL antibodies on sections from a tissue microarray. NCOA3, Maspin and VHL were positive in 90 %, 100 % and 35 %, of PDAC cases respectively, whereas NCOA3, Maspin and VHL expressions were positive in 3.8 %, 0 and 100 % of normal pancreatic tissue and in 15.2 %, 21.7 % and 97.8 % of chronic pancreatitis cases respectively. Significant differences were observed between PDAC and other groups regarding NCOA3, Maspin and VHL expression (p < 0.001). The H scores of NCOA3, Maspin and VHL could significantly distinguish between PDAC and normal cases with high sensitivity (90 %, 100 % and 98.75 % respectively) and specificity (100 %, 100 % and 96.23 % respectively). Similar findings were found in the distinction between PDAC and chronic pancreatitis (Sensitivity: 90 %, 95.25 % and 98.75 %; specificity: 100 %, 100 % and 93.48 % for NCOA3, Maspin and VHL respectively). In conclusion, NCOA3 and Maspin were found to be significantly expressed in PDAC compared to non-tumorous tissue while VHL was significantly expressed in non-tumorous tissue. A panel of NCOA3, Maspin and VHL could potentially distinguish PDAC from non-tumorous pancreatic tissue.

Fibroblast activation protein (FAP) expression in CK5/6 expressed (Basal subtype) & CK20 expressed (Luminal subtype) urothelial bladder carcinoma: an immunohistochemical study.

Urinary bladder cancer incidence varies all over the world. Egypt displays high incidence rates. Molecular subtyping helps risk stratification and personalized treatment. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment may provoke tumor-promotion or tumor suppression. Fibroblast activation protein (FAP) is a marker of CAFs, suggested to accelerate tumor progression in various cancers. In urothelial carcinoma, investigations regarding impact of FAP expression on prognosis are needed. This work aims to study impact of FAP expression in urothelial carcinoma and find its relation to CK 5/6 (basal) expressed and CK 20 (luminal) expressed immunohistochemical markers. This retrospective study included 70 urothelial carcinoma specimens. Immunohistochemistry was performed and results were analyzed. FAP was expressed in 67.1% of cases and showed significant association with advanced tumor stage, muscle invasion, mitoses in tumor cells and stratified groups; as 73.9% of FAP positive cases were of Ck5/6+/Ck20- (basal subtype). All studied parameters did not show significant association with patient's overall survival. In conclusion, FAP could have a role in modulating tumor microenvironment and promoting tumor invasion. FAP is correlated with basal subtype of urothelial carcinoma, which may be an indicator of tumor aggressiveness. FAP antagonists may be helpful in preventing tumor progression.

Comparative study of immunohistochemical expression of ERG and MAGI2 in prostatic carcinoma.

Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2. MATERIALS AND METHODS: This study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index. RESULTS: Revealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2. CONCLUSION: This study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.

Role of SIX1, EYA2, and E-cadherin in ovarian carcinoma. Evidence on epithelial-mesenchymal transition from an immunohistochemical study.

This study aims to investigate the expression of SIX1, EYA2, and E-cadherin in ovarian cancer (OC). It was conducted on 97 cases of surface epithelial tumors (SEOTs). Immunohistochemistry (IHC) staining for the three markers was applied to archival paraffin-embedded sections. Results of semi-quantitative scoring were statistically compared, correlated with clinic-pathologic parameters, response to therapy and with patient survival. RESULTS: There was a significant association of SIX1 expression in the intratumoral stroma (ITS) with malignant cases (P < 0.0001). There was a significant direct correlation between tumour cell expression of SIX1 and EYA2 (P = 0.03) and an inverse correlation between SIX1 and E-cadherin (P = 0.03). Additionally, there were direct correlations between SIX1 expression and larger tumour size (P = 0.05), high mitosis (P < 0.0001), and advanced FIGO stage (P = 0.06), and between EYA2 expression and LN metastasis (P = 0.02), and low apoptotic index (P = 0.007). Only SIX1 expression in ITS affected the patient survival by univariate analysis (P = 0.004). CONCLUSIONS: SIX1/EYA2 complex may have a poor prognostic role in OC. SIX1 expression in ITS may be used as a predictive marker of stromal invasion in ovarian borderline tumors and could affect patients' survival in OC. SIX1, EYA2, and E-cadherin may constitute a pathway that could be targeted to stop the progression of SEOTs.

Expression and clinical significance of ghrelin in endometrial hyperplasia and carcinoma of Egyptian patients.

Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p = 0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.

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, κ = 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 (κ = 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.

Case Report: Multifocal non-invasive follicular thyroid neoplasm with papillary-like nuclear features presenting in a female child.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a separate entity by the World Health Organization in 2017 with strict inclusion and exclusion criteria.  Most NIFTP cases have been reported in adults and few cases have been diagnosed in children. Here, we present a classic case of NIFTP affecting a 10-year old female child. We also review previous reports of NIFTP in children regarding size, focality, nodal metastasis, recurrence, type of operation and follow-up data. The present report adds a new case of NIFTP in the paediatric age group characterized by multifocality, absence of nodal invasion and indolent course until last follow-up, recommending less aggressive management.

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin- Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients. METHODS: Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer. RESULTS: Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients. CONCLUSIONS: High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.

Fine-Needle Aspiration Cytology of Follicular Dendritic Cell Sarcoma of Cervical Lymph Node: A Challenging Diagnosis.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor that could arise in both nodal and extranodal sites, with only nine previously reported cases demonstrating cytologic features. In this report, we describe a case of FDCS in a 60-year-old female who presented with neck mass. Fine-needle aspiration cytology and subsequent core biopsy were suggestive of metastatic carcinoma. The cytologic features were epithelioid-to-spindle cell morphology, vesicular nuclei, prominent nucleoli, intranuclear inclusions, and occasional binucleated and multinucleated forms. However, absence of cytokeratin expression was against the diagnosis of metastatic carcinoma. The definitive diagnosis was reached by the demonstration of CD21 and CD23 expression. The pathologist should be aware of this rare malignant tumor, especially its cytologic features in aspirated material. The differential diagnosis in the above case was metastatic carcinoma, melanoma, and malignant granular cell tumor. The demonstration of expression of one or more dendritic cell marker is the clue for the diagnosis, which could be applied on cytological preparations with sufficient material.

Evaluation of the Role of ALDH1 as Cancer Stem Cell Marker in Colorectal Carcinoma: An Immunohistochemical Study.

INTRODUCTION: Colorectal Carcinoma (CRC) is the third most commonly diagnosed cancer in males. Stem Cells (SC) may be involved in tumour growth, including colon cancer. Aldehyde Dehydrogenase 1 (ALDH1) is a detoxifying enzyme that might modulate SC proliferation. AIMS: To evaluate the immunohistochemical expression of ALDH1 as stem cell marker in the pathogenesis of colorectal carcinoma. MATERIALS AND METHODS: This retrospective study included 71 colorectal specimens (49 colorectal carcinoma, 13 adenoma and 9 normal cases) that were collected from Pathology Department, Faculty of Medicine, Menoufia University during the period from 2011 to 2015. All cases were stained by ALDH 1 antibody. Survival data were available for 31cases. RESULTS: There was a statistical significant association between epithelial positivity of ALDH1 and younger age (p=0.003), right sided tumour (p=0.038), presence of lymph node invasion (p= 0.04), ulcerating gross picture (p=0.01) and presence of vascular invasion (p=0.05). Moreover, there was statistical significant association between stromal positivity of ALDH1 and smaller tumour size (p=0.03) and inverse association between stromal expression of ALDH1 and grade of tumour (p=0.000) and perineural invasion (p= 0.05). Furthermore, there was an inverse significant relation between CD44 and ALDH1 expression (p=0.001). Univariate recurrence free survival analysis revealed the bad prognostic impact of high grade (p=0.03) and female sex (p=0.02) on patient outcome. CONCLUSION: Epithelial expression of ALDH1 might be associated with poor prognosis while its stromal expression might be associated with good prognosis.

The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions.

BACKGROUND AND AIM: Distinction of small-sized hepatocellular carcinoma (HCC) from dysplastic nodules may be difficult. In addition, distinction of well-differentiated HCC (WD-HCC) from high-grade dysplastic nodule (HGDN) is also difficult in small needle biopsy. We aimed to study serine peptidase inhibitor, Kazal type 1 (SPINK1) immunohistochemical expression in HCC to differentiate it from nonmalignant lesions. METHODS: This study included 179 specimens from the archival material of Pathology Department, National Liver Institute, Menoufia University, between 2007 and 2014, divided as 93 HCC and 86 nonmalignant lesions. All cases were stained for SPINK1 antibody. RESULTS: SPINK1 was expressed in 76.3% of HCC cases with a diagnostic accuracy of 79.3%.There was a significant difference between focal nodular hyperplasia and WD-HCC cases regarding mean value of SPINK1 expression (P=0.015). In addition, there was low SPINK1 score in cirrhosis cases compared with WD-HCC. Moreover, there was a high significant difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001), with 83.3% sensitivity and 84.6% specificity. CONCLUSIONS: SPINK1 can be used to differentiate between a WD-HCC and a HGDN with high diagnostic validity.

The Predictive and Prognostic Role of Topoisomerase IIα and Tissue Inhibitor of Metalloproteinases 1 Expression in Locally Advanced Breast Carcinoma of Egyptian Patients Treated With Anthracycline-based Neoadjuvant Chemotherapy.

PURPOSE: Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS). RESULTS: Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1-) was significantly associated with good response to chemotherapy in breast (P=0.006). CONCLUSION: TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.

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.

The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (p<0.001 for all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3-14.6, and p<0.001). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.

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.

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.

Relationship of CK8/18 expression pattern to breast cancer immunohistochemical subtyping in Egyptian patients.

The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expression analysis. The aim of this study was to investigate the relationship of CK8/18 to the biology of breast carcinoma (BC) represented by its IHC subtypes. The IHC expression of CK8/18 was correlated with IHC subtypes of BC using ER, PR, HER2/neu, and Ki67 LI (with cutoff 14%). All cases showed CK 8/18 expression in tumour cells with varying degree of intensities; 49/70 cases (70%) showed diffuse cytoplasmic expression (loss of membranous pattern), while 21/70 cases (30%) showed membrano-cytoplasmic pattern. Adjacent non-neoplastic breast lobules showed membrano-cytoplasmic pattern in 58% of cases, which was significantly different from the pattern in invasive cancer (P = 0.002). A loss of membranous pattern in malignant tumours was significantly associated with higher tumour grade (P = 0.02), higher mitotic count (P = 0.03), and negative HER2/neu status (P = 0.04). CK 8/18 H score ranged between 1 and 290 with mean ± SD was 181 ± 70.54. Tumours with lower CK 8/18 H score were in the advanced stage group (P = 0.04). Low CK8/18 H score and loss of membranous pattern were significantly associated with triple negative (TN) subtype as compared with luminal subtype (P = 0.006 and P = 0.026, respectively). In addition, CK8/18 with lost membranous pattern was significantly associated with TN subtype compared with HER2/neu positive subtype (P = 0.001). However, there was no significant difference between luminal A and B subtypes regarding CK8/18 H score or pattern of expression. This study concluded that low CK8/18 H score and loss of membranous pattern of CK8/18 are associated with worse prognostic features and TN subtype.