Immunoreactive Tumor Cells Research Articles

Adenoid basal carcinoma cervix – A rare epithelial neoplasm

ABSTRACT Adenoid basal carcinoma of the uterine cervix is a rare epithelial neoplasm. Adenoid basal carcinoma constitutes less than 1% of all cervical adenocarcinomas and has a favorable prognosis. Adenoid basal carcinoma is assumed to arise from a multipotential basal or reserve cell layer in the cervical epithelium. We report a case of adenoid basal carcinoma of the uterine cervix with complaints of bleeding per vagina in a 40-year-old female. The carbohydrate antigen 125 level was elevated (100 U/ml), and the MRI abdomen and pelvis revealed increased signal intensity in the anterior lip of the cervix. The local examination revealed thickening of the anterior lip of the cervix and induration in the left fornix. The patient was diagnosed with carcinoma cervix stage IB2 (FIGO Stage). The patient was operated by a radical robotic hysterectomy. Microscopic examination revealed small basaloid tumor cell nests with peripheral cell palisading and microcyst formation. The tumor cells showed p63 immunoreactivity in basaloid tumor cells and were negative for CD117 and S-100P. This tumor should be differentiated from adenoid basal cell hyperplasia, which has a favorable outcome, and adenoid cystic carcinoma, with a dismal course.

Clinicopathological Spectrum of Thyroid Swelling: A Single Institutional Prospective Study from Northeast India

Purpose: The pathologic lesions of the thyroid gland are manifested by varied morphologies. The current study aims to report the clinicopathologic features of patients with thyroid swelling from a tertiary centre of North-East India with particular emphasis on histopathological examination (HPE).Method: It is a prospective hospital-based study. Fifty-three resected specimens of thyroid surgery were included in the study. All the specimens were undertaken for HPE, and the malignant cases were subjected to immunohistochemistry (IHC). Results: Female preponderance (84.9%) of the disease was found with a maximum incidence between the age group younger than 40 (60.37%). 86.8% of cases were benign on HPE; colloid goitre reported a maximum number (62.3%). Only seven cases were found malignant, and six out of them were papillary carcinoma. All the six papillary carcinomas and one follicular carcinoma showed immunoreactivity of tumour cells to TTF 1, CK 7 and Thyroglobulin.Conclusion: Asymptomatic thyroid swelling is a prevalent entity, and the incidence of malignancy in the current study is 13.2%. Identifying malignant thyroid swelling out of the common benign or apparently benign goitres has always been problematic, and preoperative fine-needle aspiration cytology followed by HPE and IHC plays a significant role.

The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Epithelial and Stromal Characteristics of Primary Tumors Predict the Bone Metastatic Subtype of Prostate Cancer and Patient Survival after Androgen-Deprivation Therapy.

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

The expression of BMP, integrin, ZEB2 in ovarian high-grade serous carcinoma in relation with lymph node metastasis

Ovarian cancer (OC) is clinically important because it is diagnosed late and has metastasis when it is diagnosed. Mortality risk increases 2.75 times in the presence of lymph node (LN) metastasis. During metastasis, many molecules including BMPs originated from stroma, and tumor cells participate through transcription factors and integrins for cytoskeleton regulation during cell migration. We hypothesized an inverse correlation between BMP2 and BMP7 along with changes in ZEB2, and integrin α5β1 in high-grade OCs in relation to LN metastasis. The BMP2 immunoreactivity was strong along with strong ZEB2 and weak integrins’ immunoreactivity in samples with LN metastasis. Strong immunoreactivity of BMP7 was accompanied by strong immunoreactivity of integrins in the samples without LN metastasis. Study results showed BMP2’s strong positive immunoreactivity and weak BMP7 immunoreactivity in tumor cells with a significantly weak inverse correlation. This inverse correlation should be considered as both BMPs have different effects in the window of cancer progression and invasion.

Undifferentiated pleomorphic sarcoma of the breast with neoplastic fever: case report and genomic characterization

PurposePrimary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup.MethodsA 58-year-old female presented with general malaise, fever spikes, weight loss, and a massively swollen left breast. C-reactive protein and blood leucocytes were significantly increased. However, repeated blood cultures and smears were all sterile. Histopathology of the abscess-forming tumor revealed an undifferentiated malignancy with numerous of tumor giant cells as well as spindle-shaped cells with nuclear pleomorphism and hyperchromasia. Immunohistochemistry demonstrated partial, patchy desmin staining and weak heterogonous neuron-specific enolase immunoreactivity of tumor cells, but a focal staining for Melan-A.ResultsNeither common melanoma driver mutations nor an ultraviolet mutational signature was detected by whole genome sequencing. Using FISH and RT-PCR we also excluded translocations characteristic for clear cell sarcoma. Thus, the diagnosis of inflammatory UPS-NF of the breast was considered highly probable. Despite a complete mastectomy, the tumor recurred after only three months. This recurrence was treated with a combination of ipilimumab and nivolumab based on the primary tumor’s TPS score for PD-L1 of 30%. After an initial response, however, the tumor was progressive again.ConclusionWe describe here the first case of UPS-NF of the breast, which shows great clinical and histopathologic resemblances to previously reported UPS-NF of other anatomic localizations.

Evaluation of PD-L1 Expression in Undifferentiated Pleomorphic Sarcomas, Liposarcomas and Chondrosarcomas.

Immune checkpoint inhibitors (ICIs) such as PD1/PD-L1 blockers are an established treatment for many solid cancers. There are currently no approved ICIs for sarcomas, but satisfactory results have been seen in some patients with disseminated disease in certain histological types. Most studies on PD-L1 in sarcoma have used small specimens and there are no clear cutoff values for scoring. We investigated PD-L1 immunoreactivity in high-grade chondrosarcomas (CS), abdominal liposarcoma (LS) and undifferentiated pleomorphic sarcomas (UPS). In total, 230 tumors were stained with SP142 and SP263 assays and evaluated by two clinical pathologists. Immunoreactivity in tumor and immune cells was correlated with clinical outcome. Overall, ≥1% PD-L1 immunoreactivity in tumor cells was found in 11 CS, 26 LS and 59 UPS (SP142 assay) and in 10 CS, 26 LS and 77 UPS (SP263 assay). Most tumors exhibited ≤10% PD-L1 immunoreactivity, but a subset across all three subtypes had >50%. Kaplan–Meier survival analysis showed no significant difference in metastasis-free or overall survival in relation to PD-L1 immunoreactivity in tumor or immune cells for any subtype. As there is a lack of clinical data regarding PD-L1/PD-1 status and therapy response, it is not currently possible to establish clear cutoff values. Patients with high (>50%) PD-L1 immunoreactivity in tumor cells (TC) with the SP263 assay would be a logical group to investigate for potentially beneficial PD1/PD-L1-targeted treatment.

Frozen Section in Diagnosis of Thyroid Swelling: Does It Still Have Role?

Purpose The present study correlates the frozen section diagnosis of thyroid swelling with the histopathological diagnosis and assesses the expression of immunohistochemical markers in malignant thyroid tumours. Also, the study aims to analyse the accuracy and limitations of the frozen section as an intraoperative tool for the diagnosis of thyroid swellings. Method Fifty-three cases of thyroid swelling were included in the study. Frozen section reports were classified as benign, malignant and deferred. A correlation between frozen section and histopathology examination (HPE) reports has been evaluated. The malignant cases confirmed on HPE were subjected to Immunohistochemistry (IHC) with TTF-1, Thyroglobulin, and CK-7. Results Among the 53 patients, 45 (84.9%) were females, and the majority were younger than 40years (60.37%). On frozen section majority, 42 (79.25%) were benign, while a definitive diagnosis of malignancy was made in six cases (11.32%). On the frozen section, there were no false-positive cases, six true-positive cases, one false-negative case and 46 true-negative cases, with a sensitivity of 85.71%, specificity of 100%, the positive predictive value of 100%, the negative predictive value of 97.87% and diagnostic accuracy of 98.11% respectively. All the six papillary carcinomas and one follicular carcinoma showed immunoreactivity of tumor cells to TTF 1, CK 7 and Thyroglobulin. Conclusion There was a strong correlation between the frozen section and histopathological diagnosis. Still, it is not recommended in routine use for intraoperative diagnosis of thyroid swelling because of various limitations and the high diagnostic accuracy of FNAC. Adequate histopathologic diagnosis of thyroid disease is based on extensive subsampling of the specimen, which is not possible during an intraoperative frozen section procedure. If the frozen section is used, its limitations must be recognized, preferably based on first-hand data.

Glucose Transporter 4 and Interleukin 8 expression in hormone receptor negative/HER2 overexpressing breast carcinoma subtype: Correlation with biological behavior of the tumor cells and prognostic parameters

Background: Breast carcinoma (BC) is the most commonly occurring cancer. Nearly 15–20% of breast carcinomas are HER2 overexpressing subtype. Patients with this subtype have a poor prognosis with fewer therapeutic options. Increased glucose transporters expression is crucial for enhancing glucose uptake observed in several tumors. Overexpression of IL-8 has been found in neoplastic epithelial cells of various malignancies which are involved in tumor cell proliferation and invasion. Aim: Study the immunohistochemical (IHC) expression of GLUT4 and IL-8 in ER-, PR-/HER2+ BC subtype to correlate their expression with the biological behavior of tumor cells and prognosis. Materials & Methods: Fifty-eight ER-,PR-/HER2+ primary invasive ductal breast carcinoma NOS paraffin blocks were collected from archive of Patholohy department, Faculty of medicine, Tanta University and private labs. Cut sections were stained with primary anti-GLUT4, anti-IL-8, and anti-Ki67 antibodies. Results: High GLUT4 expression was significantly associated with advanced TN staging and lympho-vascular invasion (LVI). A significant relationship was found between high IL-8 immuno-expression and TN staging and LVI. A significant positive correlation was observed between high GLUT4 and IL-8 expressions on one hand and positive Ki67 immunoreactivity in tumor cells on the other hand. No statistically significant association was detected between either GLUT4 or IL-8 expression and patient age, tumor grade, or M stage. Conclusion: GLUT4 and IL-8 expression in ER-,PR-/HER2+ BC were associated with poor prognostic parameters, thus downregulation of GLUT4 and IL-8 might provide alternative therapeutic choices for patients with this subtype.

Role of CD44 and CD8 in Colorectal Adenocarcinoma metastatic

Colorectal adenocarcinoma is one of the most prevalent malignancies worldwide. The presence of regional lymph node metastases is an important prognostic indicator in colorectal adenocarcinoma. CD44 is a transmembrane protein and a cancer stem cell biomarker that plays a role in tumor proliferation, metastasis, and recurrence. The tumor microenvironment has a vital role in the stage of tumor development. CD8 is one of microenvironment's component which kills the tumor cells. This study aimed to analyze the expression of CD44 and CD8 and investigated their association with colorectal adenocarcinoma metastatic. This study's benefit is that the resulting study can be used as a prognostic factor in colorectal adenocarcinoma. This study included 56 paraffin blocks of patients diagnosed as colorectal adenocarcinoma during January 2017-December 2018 in Anatomic Pathology Laboratory Dr. Soetomo Hospital Surabaya. The paraffin blocks were sliced and stained with immunohistochemistry for CD44 and CD8. The parameters were a positive percentage of tumor cell and lymphocyte immunoreactivity against CD44 and CD8 antibodies. The percentage of CD44 is higher in the metastatic group, and the percentage of CD8 is higher in the non-metastatic group. There was a significant negative correlation between CD44 and CD8 expression in regional lymph nodes metastatic. These results indicated that CD44 and CD8 have a vital role in the incidence of metastasis.

Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma.

Pheochromocytomas (PHEOs) are relatively rare catecholamine-producing tumors derived from adrenal medulla. Tumor microenvironment (TME) including neoangiogenesis has been explored in many human neoplasms but not necessarily in PHEOs. Therefore, in this study, we examined tumor infiltrating lymphocytes (CD4 and CD8), tumor associated macrophages (CD68 and CD163), sustentacular cells (S100p), and angiogenic markers (CD31 and areas of intratumoral hemorrhage) in 39 cases of PHEOs in the quantitative fashion. We then compared the results with pheochromocytoma of the adrenal gland scaled score (PASS), grading system for pheochromocytoma and paraganglioma (GAPP) and the status of intra-tumoral catecholamine-synthesizing enzymes (TH, DDC, and PNMT) as well as their clinicopathological factors. Intratumoral CD8 (p = 0.0256), CD31 (p = 0.0400), and PNMT (p = 0.0498) status was significantly higher in PHEOs with PASS <4 than PASS ≧4. In addition, intratumoral CD8+ lymphocytes were also significantly more abundant in well-than moderately differentiated PHEO according to GAPP score (p = 0.0108) and inversely correlated with tumor size (p = 0.0257). Intratumoral CD68+ cells were significantly higher in PHEOs with regular or normal histological patterns than those not (p = 0.0370) and inversely correlated with tumor size (p = 0.0457). The status of CD163 was significantly positively correlated with that of CD8 positive cells (p = 0.0032). The proportion of intratumoral hemorrhage areas was significantly higher in PHEOs with PASS ≧4 (p = 0.0172). DDC immunoreactivity in tumor cells was significantly positively correlated with PASS score (p = 0.0356) and TH status was significantly higher in PHEOs harboring normal histological patterns (p = 0.0236) and cellular monotony (p = 0.0219) than those not. Results of our present study did demonstrate that abundant CD8+ and CD68+ cells could represent a histologically low-scored tumor. In particular, PHEOs with increased intratumoral hemorrhage should be considered rather malignant. In addition, abnormal catecholamine-producing status of tumor cells such as deficient PNMT and TH and increased DDC could also represent more aggressive PHEOs.

Giant cell angiofibroma of pelvis

Giant cell angiofibroma (GCA) is a rare, soft-tissue neoplasm that has a tendency to arise from the mesenchymal tissues of the head and neck, especially involving the orbital region. It is a benign neoplasm characterized by the presence of multinucleated stromal giant cells and angiectoid spaces. GCA belongs to the group of solitary fibrous tumor with histomorphological features intermediate between those of solitary fibrous tumor and giant cell fibroblastoma. CD34 immunoreactivity of tumor cells carries potential diagnostic value. Recurrence after the complete surgical excision is rare. We report the case of a 62-year-old male who presented with complaints of pain and heaviness in the lower abdomen. On computed tomography, a well-defined solid cystic mass was observed in the pelvis. Surgical resection was done, and the histopathological and immunohistochemical examination findings rendered the diagnosis of GCA. The patient had an uneventful postoperative period.

Stage-dependent Increase in Expression of miR-155 and Ki-67 and Number of Tumour-associated Inflammatory Cells in Folliculotropic Mycosis Fungoides.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early-vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.

Glypican 3-Targeted Therapy in Hepatocellular Carcinoma.

Glypican-3 (GPC3) is an oncofetal glycoprotein attached to the cell membrane by a glycophosphatidylinositol anchor. GPC3 is overexpressed in some kinds of tumors, particularly hepatocellular carcinoma (HCC). The prognostic significance of serum GPC3 levels and GPC3 immunoreactivity in tumor cells has been defined in patients with HCC. In addition to its usefulness as a biomarker, GPC3 has attracted attention as a novel therapeutic target molecule, and clinical trials targeting GPC3 are in progress. The major mechanism of anti-GPC3 antibody (GPC3Ab) against cancer cells is antibody-dependent cellular cytotoxicity and/or complement-dependent cytotoxicity. Since GPC3Ab is associated with immune responses, a combination of protocols with immune checkpoint inhibitors has also been investigated. Moreover, some innovative approaches for GPC3-targeting therapy have emerged in recent years. This review introduces the results of recent clinical trials targeting GPC3 in HCC and summarizes the latest knowledge regarding the role of GPC3 in HCC progression and clinical application targeting GPC3.

Tumor-specific Expression of Insulin-like Growth Factor II mRNA-binding Protein 3 Independently Predicts Worse Survival of Patients With Adenocarcinoma of the Ampulla of Vater.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) plays an important role in the adhesion, invasion, and metastasis of tumor cells. Although emerging evidence suggests that IMP3 promotes tumor progression in several malignancies, the expression of IMP3 and its prognostic implication in adenocarcinoma of the ampulla of Vater (AVAC) has not been clarified to date. The IMP3 expression status in 87 AVAC tissues was examined using immunostaining, and its association with various clinicopathological features and outcome of patients with AVAC was investigated. The vast majority (87.4%) of AVAC cases displayed at least focal cytoplasmic and membranous IMP3 immunoreactivity in tumor cells, whereas IMP3 expression was consistently absent from normal biliary epithelial cells. Tumor-specific IMP3 expression was associated with submucosal and pancreatic invasion, which were not identified in the corresponding hematoxylin and eosin-stained slides. This finding led to up-staging of the pathological tumor stage in two cases of well-differentiated AVAC. In addition, high IMP3 expression was significantly associated with a poorly differentiated histology (p=0.026). Survival analyses revealed that high IMP3 expression independently predicted shorter recurrence-free (p=0.003) and overall (p=0.029) survival. Our study demonstrated tumor-specific IMP3 expression in AVAC, which will be helpful in determining invasion depth and tumor extent in patients with well-differentiated tumors, as well as indicating worse survival of patients with AVAC. Our data highlight IMP3 expression status as a potential diagnostic and prognostic marker for AVAC.

Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum.

Histopathological characteristics of needle core biopsy and surgical specimens from patients with solitary hepatocellular carcinoma or intrahepatic cholangiocarcinoma.

BACKGROUNDPathological manifestations of hepatic tumours are often associated with prognosis. Although surgical specimens (SS) can provide more information, currently, pre-treatment needle core biopsy (NCB) is increasingly showing important value in understanding the nature of liver tumors and even in diagnosis and treatment decisions. However, the concordance of the clinicopathological characteristics and immunohistochemical (IHC) staining between NCB and SS from patients with hepatic tumours were less concerned.AIMTo introduce a more accurate method for interpreting the IHC staining results in order to improve the diagnostic value of hepatic malignancy in NCB samples.METHODA total of 208 patients who underwent both preoperative NCB and surgical resection for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between 2008 and 2015 were enrolled in this study. The expression of CK19, GPC3, and HepPar1 were detected by IHC staining. Clinicopathological, NCB, and surgical data were collected and analysed using χ2 and kappa statistics.RESULTSMorphologically, the presence of compact tumour nests or a cord-like structure in NCB was considered the primary cause of misdiagnosis of HCC from ICC. The kappa statistic showed a moderate agreement in histomorphology (k = 0.504) and histological grade (k = 0.488) between NCB and SS of the tumours. A 4-tier (+++, ++, +, and -) scoring scheme that emphasized the focal neoplastic cell immunoreactivity of tumour cells revealed perfect concordance of CK19, GPC3 and HepPar1 between NCB and SS (k = 0.717; k = 0.768; k = 0.633). Furthermore, with the aid of a binary classification derived from the 4-tier score, a high concordance was achieved in interpreting the IHC staining of the three markers between NCB and final SS (k = 0.931; k = 0.907; k = 0.803), increasing the accuracy of NCB diagnosis C (k = 0.987; area under the curve = 0.997, 95%CI: 0.990-1.000; P < 0.001).CONCLUSIONThese findings imply that reasonable interpretation of IHC results in NCB is vital for improving the accuracy of tumour diagnosis. The simplified binary classification provides an easy and applicable approach.

PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma.

Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.

Expression of PCNA, CD-31 and HER-2 in Serbian patients with oral squamous cell carcinoma

Several studies have investigated the expression of tumor markers, including p53, HER-2, PCNA, EGFR, VEGFR CD-31 and Bcl-2 in patients with oral squamous carcinoma (OSC). This study aimed to determine the expression of proliferating cell nuclear antigen (PCNA), endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31) and human epidermal growth factor receptor-2 (HER-2) according to OSC stage. The prospective study included 62 patients diagnosed with OSC stages II and III. Surgical specimens were obtained from tumor and peritumoral tissues. We determined the pathohistological degree of tumor differentiation and the immunohistochemical expression of PCNA, CD-31 and HER-2 for each specimen. Immunohistochemical analysis of the expression of PCNA in tumor cells demonstrated poor staining of immunoreactive tumor cells in 23 patients (10 in stage II, 7 in stage IIIa and 6 in stage IIIb). Moderately expressed PCNA-immunoreactivity in the tumor cells in 17 patients (7 in stage II, 6 in stage IIIa and 4 in stage III), and extremely strong PCNA-immunoreactive staining in tumor cells of 10 patients with IIIb stage, was observed. These results suggest that PCNA expression combined with pathohistological findings could possess a prognostic value in determining the survival rates for patients with oral squamous cell carcinoma.

Higher nuclear EGFR expression is a better predictor of survival in rectal cancer patients following neoadjuvant chemoradiotherapy than cytoplasmic EGFR expression.

The aim of the present study was to investigate the prognostic value of cytoplasmic (−C) and nuclear epidermal growth factor receptor (EGFR-N) expression in rectal cancer patients following neoadjuvant concurrent chemoradiotherapy (CCRT). A total of 172 newly diagnosed rectal cancer patients post-neoadjuvant CCRT and curative surgery, treated between January 1998 to December 2008, were included. Pathological tissues used for evaluation were biopsy specimens obtained prior to CCRT, and specimens collected at surgery. EGFR expression in the nucleus and cytoplasm was assessed by immunohistochemistry tests. An intensity of 3+ EGFR reactivity in the cytoplasm (and/or membrane) of tumor cells was defined as overexpression of EGFR-C. The cutoff percentage of immunoreactive tumor cells for EGFR-N overexpression was 50%. Expression levels of EGFR-C and EGFR-N were further analyzed by clinicopathological features for 5-year survival disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). The results revealed that 20.9 and 23.3% of the cohort had high EGFR-N and EGFR-C expression, respectively. EGFR-N overexpression was significantly associated with advanced pre-treatment tumor stage (T3 and 4; P=0.017) and post-treatment tumor stage (T3 and 4; P<0.001). In univariate analysis, EGFR-N overexpression was significantly associated with poorer DSS (P=0.0005), MeFS (P=0.0182), and LRFS (P=0.0014). Furthermore, it remained an independent prognosticator of worse DSS [P=0.007, hazard ratio (HR)=2.755] and LRFS (P=0.0164, HR=3.026) in multivariate analysis. Overexpression of EGFR-N, and not EGFR-C, may help identify rectal cancer patients who have an increased risk of local recurrence and poor survival following neoadjuvant CCRT.