Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study.

Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.

The effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes in patients with breast cancer.

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.

New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.

Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases.

Objective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.

STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

SPECT/CT Lymphoscintigraphy Accurately Localizes Clipped and Sentinel Nodes After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer.

PURPOSE: The aim of this study was to evaluate the impact of SPECT/CT lymphoscintigraphy on targeted axillary dissection (TAD) in node-positive breast cancer (BC) patients who had undergone neoadjuvant chemotherapy (NAC). METHODS: Sixty-two female BC patients with biopsy-confirmed axillary nodal metastases underwent NAC, followed by breast surgery with TAD. A metallic clip was placed in the sampled LN before NAC. On the day of surgery, a periareolar intradermal 99m Tc-nanocolloid injection was administered, followed by SPECT/CT lymphoscintigraphy. The clipped nodes were localized on CT images, assessed for 99m Tc uptake before surgery, and confirmed during the procedure. RESULTS: T1-4, N1-2 patients were enrolled in the study. All patients underwent sentinel lymph node (SLN) biopsy. The clipped node was the SLN in 54 (88.5%) patients. In 3 patients (4.9%), a clip was found in a nonsentinel lymph node. In 4 patients, the clips were not visible on SPECT/CT images, and lymph nodes were not found during the procedure. SPECT/CT correctly localized the clipped lymph node in all patients. The overall false-negative rate for TAD was 3.33%. The mean follow-up duration was 29 months, and there were no axillary recurrences. CONCLUSIONS: SPECT/CT lymphoscintigraphy can accurately localize clipped nodes and SLNs after NAC in patients with node-positive BC.

The gingiva contains leptin and leptin receptor in health and disease.

The presence of leptin (OB) and soluble OB receptor (s-OB-R) in gingival tissue extract and gingival crevicular fluid has led the studies investigating the relationship between OB and periodontal diseases. This study aims to investigate the levels of OB and s-OB-R in serum and their presence in gingiva of healthy controls (HC), gingivitis (G), aggressive periodontitis (AP), and chronic periodontitis (CP) patients; and whether correlations exist between clinical and serum parameters, OB and s-OB-R. Seventy-seven subjects [HC (n = 20), G (n = 20), CP (n = 21), and AP (n = 16)] were included in this study. After the clinical periodontal parameter recordings and venous blood sampling, gingival tissues obtained. Serum parameters' levels determined with enzyme linked immune sorbent assay; and OB and OB-R in gingiva immunohistochemically. No significant differences were observed regarding the serum parameters [high sensitivity C-reactive protein (hs-CRP), lipids, OB, and s-OB-R] when the groups were compared (P > 0.0125). The serum OB has positive correlations with hs-CRP in the G group (P < 0.05), and s-OB-R has presented significant negative correlations with BOP in HC group (P < 0.05), with hs-CRP in G (P < 0.05) and AP groups (P < 0.05). The positive correlations were observed between the serum OB and HDL and body mass index in the CP group (P < 0.05). In all of the tissue samples of all groups, there was positive OB and OB-R immunoreactivity in the gingival epithelium. The gingival tissues contain both OB and OB-R. The serum levels of OB and s-OB-R do not vary between patients and with different periodontal conditions.

Placental deficiency during maternal SARS-CoV-2 infection.

INTRODUCTION: Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. METHODS: This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. RESULTS: The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. DISCUSSION: The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.

Activated protein C and normal saline infusion might prevent deleterious effects of remote acute lung injury caused by intestinal ischemia-reperfusion: an experimental study in the rat model.

BACKGROUND: Intestinal ischemia-reperfusion is a common medical event associated with both clinical and experimental distant organ injury. In particular, the lung tissue appears to be susceptible to injury resulting from systemic inflammatory mediator activation. Drotrecogin α (activated) or recombinant human activated protein C has antithrombotic, anti-inflammatory, and profibrinolytic properties. We hypothesized that APC infusion would decrease lung inflammation and ameliorate lung injury resulting from intestinal ischemia-reperfusion (IIR). A rat model of intestinal ischemia-reperfusion was used to test this hypothesis, and several parameters of lung injury were measured in lung samples. MATERIAL AND METHODS: Forty Wistar albino rats were divided into four groups: a sham-operated group (Sham), an ischemic control group (IIR), an APC-infusion group (IIR'APC), and a normal saline-infusion group (IIR'NS) (n = 10, each). A marker for lipid peroxidation, malondialdehyde (MDA), free radical scavenger glutathione peroxidase (GSH-Px), an index of polymorphonuclear neutrophils, myeloperoxidase (MPO) activity, and lung polymorphonuclear leukocytes (PMNL) were investigated in the lung tissue samples. RESULTS: MDA and MPO levels, and lung PMNL sequestration were decreased, but GSH-Px levels were increased in APC treated group versus IIR group. MDA levels were decreased and GSH-Px levels were increased in NS treated group versus IIR group. MPO levels and lung PMNL counts were similar across the IIR and IIR'NS groups. CONCLUSIONS: This study documents that APC attenuates acute lung injury in intestinal ischemia-reperfusion. NS infusion had also some favorable effects regarding MDA and MPO.

Immunohistochemical galectin-3 expression in non-melanoma skin cancers.

Galectin-3 is a ss-galactoside-binding lectin. It participates in a variety of normal and pathologic processes, including cancer progression. In this study, we evaluated the pattern of expression of galectin-3 in cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and its correlation with the grade of differentiation in SCC and tumor size. Galectin-3 expression was evaluated by immunohistochemistry in 31 SCCs, 30 BCCs, and 29 non-tumoral skin samples. Galectin-3 expression was higher in normal epidermis than in non-melanoma skin cancers, except for cytoplasmic immunoreactivity in SCC. Cytoplasmic galectin-3 immunoreactivity was significantly higher than nuclear immunoreactivity in non-melanoma skin cancers. Cytoplasmic galectin-3 immunoreactivity was significantly higher in SCC than in both circumscribed and infiltrative BCCs, but no difference was detected between these two types of BCC. Cytoplasmic galectin-3 immunoreactivity predominated within SCCs (p=0.000), and a positive correlation was detected between tumor size and cytoplasmic immunoreactivity (r=0.385, p=0.043). There was no correlation between galectin-3 staining and tumor differentiation and lymph node metastasis. Decreased nuclear galectin-3 expression and cytoplasmic immunoreactivity in tumors are important factors in the progression from the normal to the cancerous state in non-melanoma skin cancers. We speculate that cytoplasmic galectin-3 expression may be one of the factors that contribute to tumor aggressiveness in SCC.

Endothelin receptor antagonism by tezosentan attenuates lung injury induced by aortic ischemia-reperfusion.

Tezosentan is a novel dual endothelin receptor antagonist. The purpose of this study was to examine the effect of tezosentan on lung injury induced by abdominal aortic ischemia-reperfusion (IR) in rats. Thirty-two Wistar-albino rats were randomized into four groups (eight per group) as follows: control group (sham laparotomy), aortic IR group (120 min ischemia and 120 min reperfusion), aortic IR + tezosentan group (a bolus intravenous injection of 10 mg/kg tezosentan before ischemia plus continuous intravenous infusion of 1 mg/kg/hr tezosentan during 120 min ischemia and 120 min reperfusion), and control + tezosentan. Blood and lung tissue samples were obtained for biochemical analysis. Protein concentrations in bronchoalveolar lavage fluid and lung wet/dry weight ratios were measured. A histological evaluation was also done. Aortic IR significantly increased (p < 0.05 vs. control group) and tezosentan significantly decreased (p < 0.05 vs. aortic IR group) the plasma level of tumor necrosis factor-alpha; lung tissue levels of malondialdehyde, catalase, and myleperoxidase; and protein concentration in bronchoalveolar lavage fluid and lung wet/dry weight ratio. Histological evaluation showed that tezosentan attenuated the morphological changes associated with lung injury. The results of this study indicate that tezosentan attenuates lung injury induced by aortic IR in rats. We propose that this protective effect of tezosentan is due to (1) reduced systemic inflammatory response, (2) reduced oxidative stress and lipid peroxidation in lung tissue, (3) reduced pulmonary microvascular leakage, and (4) inhibition of leukocyte infiltration into lung tissue.

Cyclooxygenase-2 expression in primary and recurrent pterygium.

BACKGROUND: Pterygia are common, benign, fibrovascular, and infiltrative processes of the corneo-conjunctival junction of unknown pathogenesis. Cyclooxygenase-2 (COX-2) mediates the rate-limiting step in arachidonic acid metabolism. Extensive evidence indicates that the COX-2 prostanoid pathway is involved in inflammation. The aim of the study was to document the immunohistochemical expression of COX-2 in primary and recurrent pterygia. MATERIALS AND METHODS: In this study, 21 primary pterygia and 12 recurrent pterygia from subjects undergoing pterygium surgery and six normal corneal-scleral tissue specimens were studied immunohistochemically for COX-2 expression. RESULTS: COX-2 was expressed in primary pterygia and recurrent pterygia specimens. There was a statistically significant difference in COX-2 expressions in fibroblasts between primary and recurrent pterygium cases ( P = 0.001). There were statistically significant differences in COX-2 expressions in surface epithelium ( P = 0.028) and stromal inflammatory cells ( P =0.000) between control tissues and primary pterygia tissues. We also detected statistically significant differences in COX-2 expressions in surface epithelium ( P =0.000), stromal fibroblasts P =0.000 (stromal fibroblasts and inflammatory cells), vessels ( P = 0.027) and inflammatory cells ( P =0.001) between control tissues and recurrent pterygia tissues. CONCLUSIONS: This is the first study to document the expression of COX-2 in primary and recurrent pterygia. In our opinion after excision of pterygia, fibroblastic proliferation continues and this contributes to recurrence.

Lamotrigine reduces intestinal I/R injury in the rat.

I/R injury of the intestine is a life-threatening emergency with mortality rates still more than 60%. We have investigated the protective effect of lamotrigine (LTG), an antiepileptic drug, which has an established neuroprotective effect, on intestinal I/R injury in rats. Forty-eight Wistar albino rats were divided into three groups: a sham-operated group (no I/R injury; n = 16), an ischemic control group (I/R, n = 16), and an LTG-treated group (pretreatment 5 mg kg-1 LTG + IR; n = 16). A marker for lipid peroxidation, malondialdehyde, free radical scavengers, glutathione peroxidase, catalase, and superoxide dismutase levels, an index of polymorphonuclear neutrophils, myeloperoxidase activity, and mucosal damage were investigated. Malondialdehyde levels, myeloperoxidase activity, and the severity of mucosal damage were decreased in the LTG group. Moreover, in the LTG group, glutathione peroxidase and superoxide dismutase levels were higher compared with the I/R group. The pretreatment of rats with LTG before intestinal ischemia ameliorates the mucosal damage in intestinal I/R injury probably by altering lipid peroxidation, neutrophil accumulation, and antioxidant activity.

Immunohistochemical expression of PTEN in normal, hyperplastic and malignant endometrium and its correlation with hormone receptors, bcl-2, bax, and apoptotic index.

PTEN is a tumor suppressor gene that is frequently mutated in type I endometrioid endometrial carcinomas (EECs), and is involved in the control of cell proliferation, differentiation, and apoptosis. In this study, we aimed to assess the relationship between PTEN expression and estrogen, progesterone receptors (PRs), other apoptosis-related proteins, such as bcl-2 and bax, and apoptotic index (AI) in EEC, its precursor lesion hyperplasia, and cyclical endometrium. We also evaluated the relationship between PTEN expression and clinicopathologic parameters. PTEN, estrogen receptor (ER), PR, and bcl-2 and bax expressions were evaluated immunohistochemically, and AI was evaluated in hematoxylin and eosin (HE)-stained slides in 23 cyclical and 37 hyperplastic endometria and in 35 EECs. PTEN expression was higher in cyclical endometrium than in the carcinomas (p<0.05). The PTEN expression level was significantly higher in non-atypical hyperplasias than in EEC, but there were no differences between atypical complex hyperplasia (ACH) and EEC and between hyperplasias. In the carcinomas, there was a negative correlation between grade and PTEN expression (r=-0.338, p=0.047). In conclusion, we presume that PTEN is involved in the early phases of endometrial tumorigenesis, and it can be speculated that decreased PTEN expression with loss of differentiation in carcinoma can contribute to the emergence of tumors with a more aggressive phenotype.

CD24 expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.

CD24 is a small, heavily glycosylated cell surface protein, that is expressed in a large variety of solid tumors. It is considered to play an important role in tumor progression and metastasis. We aimed to evaluate CD24 expression in invasive ductal carcinomas (IDCa), ductal carcinoma in situ (DCIS) and non-tumorous breast tissues, and to investigate the relationship between histopathological parameters, estrogen and progesterone receptors, and c-erbB2 expressions. The study included 34 IDCa, 25 DCIS, and 13 non-tumorous breast tissues. All cases were reevaluated histopathologically, and immunohistochemistry was performed with monoclonal CD24 antibody. The results clearly demonstrated that CD24 expression, including membranous and cytoplasmic staining, was significantly higher in DCIS and IDCa than in the non-tumorous breast (p=0.001, p=0.000, and p=0.035, p=0.000, respectively). Cytoplasmic staining was detected predominantly in neoplastic tissues and was significantly increased in high grade DCIS (p=0.013). In invasive carcinomas, although the level of membranous staining was significantly positively correlated with tumor grade (p=0.040), there was no such an association with the cytoplasmic level. However, it showed a trend towards pT (p=0.089). In conclusion, our results suggest that higher CD24 expression may be associated with malignant transformation and progression in breast cancer biology. Furthermore, higher membranous expression and, in particular, cytoplasmic staining seem to predict malignant transformation, and different patterns of CD24 expression may be associated with different pathological features in breast tumors.

The role of immunohistochemical adrenomedullin and Bcl-2 expression in development of type-1 endometrial adenocarcinoma: Adrenomedullin expression in endometrium.

BACKGROUND: Adrenomedullin (AM) is a pluripotent peptide first discovered from human pheochromocytoma. AM expression has been shown in various cancer types including endometrium cancer. Bcl-2 is an antiapoptotic protein which might be regulated by AM in hypoxic conditions. The aim of the present study was to investigate the role of AM and Bcl-2 expressions in carcinogenesis of type-1 endometrium cancer. MATERIALS AND METHOD: Study group consisted of 10 proliferative endometrium, 22 simple endometrial hyperplasia, 23 endometrial intraepithelial neoplasia (EIN) and 30 Grade 1 endometrioid adenocarcinoma patients. AM and Bcl-2 expressions were investigated by immunohistochemistry. RESULTS: Mean AM Allred score was 3±2.6, 5.6±1.6 and 5.7±2.5 in benign, EIN and adenocarcinoma groups, respectively. AM expression was significantly higher in EIN and adenocarcinoma groups than in benign endometrium group (p<0.05). Mean Bcl-2 Allred score was 6.4±2.1, 5.2±2.6, 2.3±2 in benign endometrium, EIN and adenocarcinoma groups, respectively. Mean Bcl-2 Allred score was similar between benign endometrium and EIN groups (p>0.05). However, it was significantly lower in adenocarcinoma group (p<0.05). An inverse correlation between AM and Bcl-2 expressions was found (r: -0.4, p<0.001). CONCLUSIONS: Our findings showed that AM expression increased in progression from benign endometrium to EIN and type-1 adenocarcinoma while expression of Bcl-2 decreased in transition from EIN to carcinoma.

The effect of tumor invasion patterns on pathologic stage of bladder urothelial carcinomas.

The aim of this study was to investigate tumor invasion pattern, its heterogeneity and association with histopathological features and stage in invasive urothelial carcinoma of the bladder. We studied 62 cases of invasive urothelial carcinoma of the bladder. World Health Organization (WHO) 1973, WHO/ISUP 1998 and WHO 1999 systems were used for tumor grading. Pathologic staging of each case was done according to 1997 TNM system. During evaluation of the slides three main tumor invasion patterns were detected: "nodular", "trabecular" and "infiltrative". In addition, homogeneity or heterogeneity of invasion patterns was also recorded for each case. Of sixty-two invasive cases, 17 (27%) had nodular, 36 (58%) trabecular, and 9 (15%) infiltrative invasion pattern. There was a statistically significant difference between invasion patterns in relation to pathologic stage (pT) (p=0.001), but not to grade. Of the 17 cases with nodular invasion pattern and 36 tumors with trabecular invasion pattern, 13 (77%) and 26 (72%) were pT1, respectively, whereas 8 of 9 infiltrative cases (89%) were advanced stage (pT2-3). According to heterogeneity, forty-two cases (68%) had homogeneous, while the remaining 20 (32%) had heterogeneous invasion pattern. Of the 42 homogeneous cases 34 (81%) were pT1, whereas 14 of 20 heterogeneous cases (70%) were advanced stage (p=0.000). The different invasion patterns seem to have a large impact on pathologic stage, especially the infiltrative pattern. In addition, invasion heterogeneity appears to be of value in determination of biologic aggressiveness in urothelial carcinoma.

The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1 expressions in invasive ductal carcinoma of the breast: CD44/CD24 expression in breast cancer.

BACKGROUND: Recently, there are several studies about cancer stem cells (CSC), indicating that they are the cells that initiate the tumor, provide progression, metastasis and responsible for the aggressive tumor behavior. MATERIALS AND METHODS: The purpose of this study is to investigate the expressions of CD24, CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma. Their relationships with clinicopathologic parameters, such as tumor grade, lymphovascular invasion, tumor size, axillary lymph node involvement, stage, hormone receptors, HER2 expression, basal like tumors, triple negative status and prognosis were also investigated. Tissue microarray method was used to investigate immunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105 invasive ductal carcinoma cases. RESULTS: CD133 expression was significantly associated with tumor size (p=0.023) and stage (p=0.009). CD133 expression was decreased in tumors with larger tumor size, higher stage and lymphovascular invasion. CD133 expression was positively correlated with CD44 (r=0.212, p=0.032) and CD44(+)/CD24(+) (r=0.202, p=0.040) expressions. CD44, CD24 and ALDH1 expressions showed no significant relationship and correlation with clinicopathologic features. There was a significant relationship (p=0.048) between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was positively correlated with CD44(+)/CD24(-/low) phenotype (r=0.211, p=0.036). CONCLUSIONS: Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low) phenotype. CD133 can detect a different population of CSC in breast carcinoma.

Immunohistochemical demonstration of the expression of CYP2E1 in human breast tumour and non-tumour tissues.

Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 2E1 (CYP2E1), a member of multigene superfamily of enzymes, plays a major role in the activation of some of these chemicals such as tobacco-derived N-nitrosamines. Using immunohistochemistry, the cellular distribution and the level of expression of CYP2E1 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP2E1 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 96% (24/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP2E1 was detected in normal epithelial, myoepithelial and to a lesser degree in some of the non-epithelial cells (e.g. endothelial cells). No positive staining was detected in other non-epithelial cells such as fibroblasts in normal breast tissues. When CYP2E1 staining was assessed semiquantitatively the mean staining score values of CYP2E1 was found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP2E1 protein is expressed in both tumour and normal breast tissue with an increased expression in breast tumours.