Low Histopathological Grade Research Articles

MicroRNA (miRNA) PROFILING IN PROSTATE CANCER CARCINOGENESIS: EXPLORATORY RESEARCH

Future research will continue to be carried out in terms of looking for molecular markers involved in the early processes of carcinogenesis, metastasis and therapeutic targets in prostate cancer patients. MicroRNAs (miRNAs) are small noncoding RNAs that contribute to prostate cancer progression by controlling genes involved in the androgen receptor (AR) signaling pathway, ectopic expression of proteins involved in the cell cycle and apoptosis, epithelial-mesenchymal transition (EMT) and metastasis of cancer stem cells (CSCs). This study was an exploratory study, the aim was to assess miRNA expression in low histopathological grade prostate cancer compared with high histopathological grade prostate cancer. The novelty of this research is to assess the 25 most increased (up-regulated) and 25 lowest (down-regulated) miRNAs from 800 types of miRNA. Next, we will analyze the mechanisms and confirm the carcinogenesis of prostate cancer. The research results can be used for further research data, especially for targeted therapy in prostate cancer patients.

Relationship between TGF-Beta 1 rs1800469 Gene Polymorphism with Degree of Tumor Invasion of Colorectal Cancer at RSUP Prof. Dr. I.G.N.G. Ngoerah Denpasar Bali

The incidence of cancer, including colorectal cancer (CRC), increases with age. The Transforming Growth Factor-Beta 1 (TGF-B1) rs1800469 gene polymorphism is associated with the pathogenesis of CRC. The T allele is associated with increased transcriptional activity compared to the C allele, meaning that individuals with TT homozygotes will produce higher TGF-B1 protein concentrations. This study aimed to analyze the relationship between the TGF-B1 rs1800469 gene polymorphism and degree of tumor invasion of CRC in Bali, especially at the RSUP Prof. Dr. I.G.N.G. Ngoerah Denpasar. This hospital study was a cross-sectional study using formalin-fixed-paraffin embedded (FFPE) samples from CRC patients, stored in the Department of Pathology Prof. Dr. I.G.N.G. Ngoerah Denpasar Bali. Identification of TGF-B1 rs1800469 polymorphism gene was performed using polymerase chain reaction (PCR) and sequencing methods. Data on age, sex, histopathological grading, degree of tumor invasion, pathological staging N and tumor location were recorded from the patient's medical record, carried out descriptive analysis and hypothesis testing of bivariate Chi Square analysis. Out of 48 samples, majority was over 50 years old (83.3%), male (54.2%), low grade histopathology (93.8%), adenocarcinoma histological classification (97.9%), high degree of tumor invasion (81.2%), staging pathology N with regional lymph nodes cannot be assessed (93.7%), left tumor location (58.3%) with TGF-B1 rs1800469 gene polymorphism CT genotype of 23 samples (47.9%), followed by TT genotypes of 17 samples (35.4%) and CC genotypes of 8 samples (16.7%). The results of the Chi Square statistical analysis test found no association between the TGF-B1 rs1800469 gene polymorphism in any genotype and degree of tumor invasion of CRC (p=0.688). It can be concluded that there was no significant relationship between the TGF-B1 rs1800469 gene polymorphism and degree of tumor invasion of CRC patients at RSUP Prof. Dr. I.G.N.G. Ngoerah, Denpasar, Bali. Keywords: Colorectal Cancer, Gene Polymorphism, SNP, Tumor Invasion

The expression of platelet-derived growth factor and its receptor in canine and feline meningiomas.

Feline meningiomas usually have benign biological behavior, while canine and human meningiomas are often classified as grade 2 or 3. Activation of the platelet-derived growth factor (PDGF) and its receptor signal pathway through PDGFβ/Rβ autocrine and paracrine is considered to play an important role in the tumor proliferation and malignant transformation of human meningiomas. However, there have been few studies about the expression of these molecules in canine meningiomas and no studies about their expression in feline meningiomas. We analyzed the PDGFα/Rα and PDGFβ/Rβ expression in canine and feline meningiomas by immunohistochemistry and western blotting. Immunohistochemically, most canine meningiomas showed the expression of PDGFα (42/44; 95.5%), PDGFRα (44/44; 100%) and PDGFRβ (35/44; 79.5%), and a few showed the expression of PDGFβ (8/44; 18.2%). In contrast, feline meningiomas were immunopositive for PDGFRα and PDGFRβ in all cases (14/14; 100%), while no or a few cases expressed PDGFα (0/14; 0%) and PDGFβ (2/14; 14.3%). Western blotting revealed specific bands for PDGFα, PDGFRα and PDGFRβ, but not for PDGFβ in a canine meningioma. In a feline meningioma, specific bands for PDGFRα and PDGFRβ were detected, but not for PDGFα and PDGFβ. These results suggested that canine meningiomas commonly express PDGFα/Rα, and thus autocrine or paracrine PDGFα/Rα signaling may be involved in their initiation and progression. Moreover, PDGF negativity may be related to benign biological behavior and a low histopathological grade in feline meningioma.

Cornulin as a Potential Novel Biomarker for Cutaneous Squamous Cell Carcinoma.

Background This study aimed to evaluate the expression of an epidermal differentiation marker, cornulin, in cutaneous squamous cell carcinoma (cSCC). Cornulin has been found to be downregulated in various squamous cell carcinomas of other tissues; however, its expression in cSCC has never been studied. We predicted that cornulin expression in cSCC is reduced compared to the normal epidermis. Moreover, we hypothesized that an inverse relationship exists between cornulin expression and the loss of differentiation, as defined by histopathological grading of cSCC lesions. Methodology Samples of normal skin and cSCC lesions of variable histopathological grades were stained using immunohistochemistry. High-resolution tissue images were analyzed with Aperio ImageScope (Leica Biosystems) utilizing a positive-pixel-counting algorithm to quantify the staining intensity. Histo-score (H-score) was calculated based on staining intensity and percentage of positive cell staining. Mean H-scores were compared using an unpaired t-test. Results We documented cornulin expression in cSCC for the first time. Cornulin levels were downregulated by more than two-fold in cSCC compared to the normal epidermis. Additionally, we observed a 4.5-fold downregulation in cornulin expression in tumors with high histopathological grades when compared to low histopathological grade tumors. Conclusions Cornulin expression levels measured through immunohistochemistry staining can help distinguish among the different histopathological grades of cSCC. Therefore, we propose that cornulin detection can be an adjunct to pathological examination to evaluate the differentiation status of cSCC specimens. Longitudinal studies are needed to establish the utility of cornulin as a diagnostic and prognostic biomarker for cSCC.

Incomplete cytoreduction with peritoneal metastases from appendiceal mucinous neoplasms.

Complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapyis the standard of care for mucinous appendiceal neoplasms with peritoneal metastases. Despite many publications regarding selection factors favoring a complete CRS, incomplete CRS does occur. Patients with an incomplete CRS are the focus of this manuscript. A retrospective analysis of prospective, histologic, and perioperative data was performed. Overall survival was the endpoint for the numerous assessments. Judgments regarding when to and when not to proceed with an incomplete CRS were sought. From a database of 949 patients who underwent an index CRS for appendiceal mucinous neoplasm, 264 patients (27.8%) had an incomplete CRS. The median overall survival was 1.8 years. Low-grade histopathology and absence of tense ascites or bowel obstruction were significantly associated with increased overall survival. More extensive surgery suggested a more favorable outcome. When a surgeon is confronted by a procedure that will inevitably end with an incomplete CRS, a current trend is to close quickly and always avoid complications. Patients with low-grade neoplasms who present in the absence of tense ascites or bowel obstruction may gain years of survival by surgical reduction of tumor burden.

Inclusion of fibroblasts and collagen fibrils in the cytologic grading of canine cutaneous mast cell tumors.

Fibroblasts and/or collagen fibrils have not been included in previous cytologic grading schemes of canine mast cell tumors (MCTs), and their association with biological behavior is broadly debated. This study aimed to evaluate the cytologic findings of canine MCT, with emphasis on the microenvironment, and propose a novel cytologic grading system correlated with mortality and histologic grade. Cytology smears of canine cutaneous MCTs were retrospectively reviewed and compared with their histopathologic counterparts using Cohen´s Kappa test. One-year survival rates were also compared with the cytologic and histopathologic variables using Pearson´s correlation test. From 92 first-occurrence canine cutaneous MCTs, the five features most associated with mortality were selected for a new grading system. The five features were cytoplasmic granulation, fibroblast and/or collagen fibril concentrations, and the presence of mitotic figures, multinucleation, and karyomegaly. Among concordant histopathologic and cytologic cases (ie, the same grades using both systems), mortality rates were 2.6% (1/38) for low-grade and 71.4% (10/14) for high-grade cases (P<0.001, chi-square). For false-negative and false-positive results, mortality rates were 33% (1/3) and 45% (5/11), respectively (P=0.707). Unlike the Camus cytologic grading system, the present amendment excluded binucleation and included fibroblasts and/ or collagen fibrils, which in higher concentrations were associated with increased survival and a low histopathologic grade. Cytologic grading with the inclusion of fibroblast and collagen fibril concentrations correlated with survival, as did the Camus cytologic and Kiupel histopathologic grades; however, further studies are needed to confirm the prognostic value of this novel cytologic grading scheme.

Inclusion of Immunotherapy in the Management of Primary and Metastatic Malignant Tumours of the Kidney Including Adult Renal Cell Carcinoma: A Review and Update

Inclusion of Immunotherapy in the Management of Primary and Metastatic Malignant Tumours of the Kidney Including Adult Renal Cell Carcinoma: A Review and Update

Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy.

Simple SummaryMetastatic prostate cancer is incurable and lethal. Tumor growth is initially reduced by radiation, surgery, or hormone therapy and later, by pairing them with chemotherapy for advanced cancer. Recent innovations have helped to develop prescription drugs against certain prostate cancer types, showing gene alterations that prevent the repair of damaged DNA or activate the body’s anti-cancer natural immune defense. A panel of genes has been identified whose cancer genome alterations may predict whether non-metastatic prostate cancer would go on to metastasize. The activity of these genes may help to guide treatment decision for non-metastatic cancer with the choice for non-aggressive versus debilitating aggressive options. The probing of prostate cancer genome has uncovered hormonal abnormalities and genome changes specific to individual patients and studies are revealing how these changes can lead to treatment failure. The discovery of new druggable vulnerabilities of the cancer cells has presented opportunities to develop precision treatments of metastatic prostate cancer tailored to individual patients.Organ-confined prostate cancer of low-grade histopathology is managed with radiation, surgery, active surveillance, or watchful waiting and exhibits a 5-year overall survival (OS) of 95%, while metastatic prostate cancer (PCa) is incurable, holding a 5-year OS of 30%. Treatment options for advanced PCa—metastatic and non-metastatic—include hormone therapy that inactivates androgen receptor (AR) signaling, chemotherapy and genome-targeted therapy entailing synthetic lethality of tumor cells exhibiting aberrant DNA damage response, and immune checkpoint inhibition (ICI), which suppresses tumors with genomic microsatellite instability and/or deficient mismatch repair. Cancer genome sequencing uncovered novel somatic and germline mutations, while mechanistic studies are revealing their pathological consequences. A microRNA has shown biomarker potential for stratifying patients who may benefit from angiogenesis inhibition prior to ICI. A 22-gene expression signature may select high-risk localized PCa, which would not additionally benefit from post-radiation hormone therapy. We present an up-to-date review of the molecular and therapeutic aspects of PCa, highlight genomic alterations leading to AR upregulation and discuss AR-degrading molecules as promising anti-AR therapeutics. New biomarkers and druggable targets are shaping innovative intervention strategies against high-risk localized and metastatic PCa, including AR-independent small cell-neuroendocrine carcinoma, while presenting individualized treatment opportunities through improved design and precision targeting.

MAML2 gene rearrangement, fusion patterns and clinicopathological characteristics in primary pulmonary mucoepidermoid carcinoma

Objective: To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC). Methods: Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed. Results: The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P<0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival (P<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions: The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

Isolation of low grade urinary bladder tumors carrying bad prognosis using KI-67 labeling index

Introduction: Even among low grade bladder tumors, there are some which have been found to carry bad prognosis for progression, recurrence and survival. Accurately pinpointing these cases at the time of diagnosis just with the help of routine histopathology is problematic. Ki-67 immunostaining may potentially be of help in identifying such cases, making administration of additional treatment modalities like chemotherapy and radiotherapy possible. There is scarcity of such studies in our country. The present study aims to correlate Ki-67 labeling index with the histopathological type and grade, pathological stage and mitotic index of urinary bladder tumors. Objective: Objective of the study is to consider the possibility of using Ki-67 labeling index to identify those low grade urinary bladder tumors which carry bad prognosis. Materials and Methods: All trans-uretheral resection of bladder tumor (TURBT) specimens in our institute were analyzed for their histopathological grade, pathological stage, mitotic index and Ki-67 labeling index in the period extending from from August 2015 to December 2016. The clinical data were analyzed retrospectively and statistically. SPSS Version 23 (SPSS Inc.,Chicago, IL, USA) software was utilized for all statistical analyses. Chi-square analysis was utilized for comparison of groups. Results with P Results: Ki-67 expression in Low grade urothelial carcinoma (LGUC) showed variation from 1.4% to 41%. The papillary urothelial neoplasm of low malignant potential (PUNLMP) cases showed variation from 16 -17%. And the only case of transitional cell papilloma in the study was found to have expression of 9%.Conclusion: Cases of high (more than 20%) Ki-67 MIB-1 labeling index can be segregated even from among those cases with low histopathological grade, low mitotic index and pTa histopathological stage. Such cases are candidates for multimodality treatment including radiotherapy, chemotherapy etc. Keywords: Bladder tumors,

Heterotopic acinic cell carcinoma and its clinical implications.

This is a review of the clinical and histopathological published data on very rare heterotopic acinic cell carcinomas (AcCCs) with suggested optimal management. Extrasalivary AcCCs originate primarily in parotid lymph nodes. They present at low clinical stage, show mostly low-grade histopathology and are circumscribed with a complete nodal capsule. Extracapsular dissection was advocated as adequate therapy. In rare cases with positive surgical margins, a completion parotidectomy or adjuvant radiotherapy should follow. Heterotopic high-grade AcCCs are rare, necessitating radical surgery including neck dissection and adjuvant radiotherapy. The short term prognosis is excellent, long term outcomes are not known. Longer term follow-up is essential.

Inhibition of matrix metalloproteinase-2 modulates malignant behaviour of oral squamous cell carcinoma cells.

Matrix metalloproteinases (MMPs) play a crucial role in the malignant phenotype of cancer cells. In particular, active levels of MMP2 in cancer cells have been associated with invasion and metastasis through the degradation of basement membrane extracellular matrix proteins. However, little is known about the role of this potential biomarker in oral cancer. Our aim was to investigate the effect of MMP2 inhibition on OSCC activity in vitro, as well as to assess MMP2 dysregulation in oral cancer samples. Human OSCC cell lines H357 and H400 were tested with the selective MMP2 inhibitor ARP101 and the MMP2 neutralising monoclonal antibody MA5-13590 to assess cell proliferation in vitro using MTS assay. Cell migration at 12/24h was assessed using a Transwell migration assay. Cell invasion was assessed at 24h using a Corning Matrigel invasion assay. MMP2 expression was assessed in 208 tissue samples (related to 60 OSCC cases and nine normal control) using tissue microarray (TMA) and further analysed via TCGA. Both ARP101 and MA5-13590 monoclonal antibody reduced cell proliferation in both the cell lines tested. Treatment with 4μg/mL of MMP2 monoclonal antibody showed a significant decrease in cell migration at 24hours. The administration of ARP101 and monoclonal antibody to H357 and H400 cell lines induced a drastic reduction in cell invasion at 24h compared to the control. In patients, TCGA analysis demonstrated that oral cancer tissues express significantly higher levels of MMP2 mRNA compared to normal oral tissues. Further, IHC analysis on TMA showed significant difference in MMP2 protein expression between low and high histopathological grade OSCC. We have demonstrated, for the first time, that MMP2 inhibition affects oral cancer cells ability to survive, migrate and invade in vitro. Differences between MMP2 expression in normal and malignant tissues varied. Further research on the role of MMP2 in OSCC and novel mechanisms to inhibit MMP2-dependent pathways should be encouraged.

Perioperative fatigue in patients with diffuse glioma

PurposeFew studies have assessed fatigue in relation to glioma surgery. The purpose of this study was to explore the prevalence of pre- and postoperative high fatigue, perioperative changes, and factors associated with pre- and postoperative high fatigue in patients undergoing primary surgery for diffuse glioma.MethodsA total of 112 adult patients were prospectively included. Patient-reported fatigue was assessed before and one month after surgery using the cancer-specific European Organization for Research and Treatment of Cancer questionnaire fatigue subscale. The scores were dichotomized as high fatigue (≥ 39) or low fatigue (< 39). A change in score of ≥ 10 was considered as a clinically significant change. Factors associated with pre- and postoperative high fatigue were explored in multivariable regression analyses.ResultsHigh fatigue was reported by 45% of the patients preoperatively and by 42% of the patients postoperatively. Female gender and low Karnofsky Performance Status (KPS) were associated with preoperative high fatigue, while postoperative complications, low KPS and low-grade histopathology were associated with postoperative high fatigue. In total 35/92 (38%) patients reported a clinically significant improvement of fatigue scores after surgery, 36/92 (39%) patients reported a clinically significant worsening of fatigue scores after surgery, and 21/92 (23%) patients reported no clinically significant change in fatigue scores after surgery. Patients with low-grade gliomas more often reported low fatigue before surgery and high fatigue after surgery, while patients with high-grade gliomas more often reported high fatigue before surgery and low fatigue after surgery.ConclusionsOur findings indicate that fatigue is a common symptom in patients with diffuse glioma, both pre- and postoperatively. Perioperative changes were frequently seen. This is important knowledge when informing patients before and after surgery.

Evaluating and Predicting the Probability of Death in Patients with Non-Metastatic Osteosarcoma: A Population-Based Study.

BackgroundOsteosarcoma is one of the most common bone tumors, with strong local aggressiveness and early metastasis. The aim of this study was to describe the epidemiological data and evaluate the prognostic factors for overall survival (OS) and cause-specific survival (CSS) in patients with non-metastatic osteosarcoma.Material/MethodsPatients histologically diagnosed with non-metastatic osteosarcoma between 2005 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning, and Lasso regression were used to identify the prognostic factors for OS and CSS, and the accuracy of the nomograms was tested and compared with the American Joint Committee on Cancer (AJCC) staging systems.ResultsThe entire cohort comprised 1000 patients with non-metastatic osteosarcoma. The multivariable analysis suggested that age, tumor size, grade, and American Joint Committee on Cancer (AJCC) T staging were independent prognostic factors for OS and CSS. Additionally, the nomograms based on these results could better predict probability of OS (Internal validation C-index, 0.7095) and CSS (0.7100) compared with the sixth (OS: 0.613; CSS: 0.628) and seventh edition AJCC staging systems (0.602, 0.613).ConclusionsRelatively young age and low histopathological grade were favorable factors for both OS and CSS. Nomograms based on multivariable models worked well in predicting the probability of death for patients with non-metastatic osteosarcoma.

Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells.

The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and CEACAM8 form heterodimers and exert their effects. Therefore, we examined the effects of CEACAM6 and CEACAM8 co-expression in breast cancer. We first studied CEACAM6/8 expression using immunohistochemistry in 109 patients with breast cancer. We then established MCF-7 cells that were stably transfected with CEACAM8 and studied cell proliferation, invasion and adhesion. The number of CEACAM6 and CEACAM8 double-positive breast carcinoma cells significantly increased in patients with low histopathological grade and stage. Proximity ligation assay (PLA) confirmed high CEACAM6/8 expression in MCF-7 cells. CEACAM6/8 expression promoted the adhesion of MCF-7 cells to endothelial cell monolayers but inhibited their invasion and proliferation. Furthermore, CEACAM6 status in carcinoma cells was significantly higher in bone than in lung metastases. CEACAM6/8 expression is associated with the inhibition of vascular invasion and cell proliferation. CEACAM6 expression was also considered to be involved in bone metastases of breast cancer. This is the first study to demonstrate the possible role of CEACAM6/8 heterodimer and CEACAM6 expression in breast cancer patients.

Magnetic resonance imaging features of gemistocytic astrocytoma.

Gemistocytic astrocytoma is the second most common subtype of World Health Organization grade 2 astrocytoma, but has a worse prognosis than other grade 2 lesions. We aim to describe the MR imaging features of histopathologically proven gemistocytic tumours. Ethics approval was obtained from both institutions. Patient consent was not required for this retrospective study. We reviewed MR imaging findings of 16 consecutive cases of histopathologically proven gemistocytic astrocytoma and anaplastic astrocytoma with gemistocytic features. Average patient age was 48years, with a 3:1 male to female ratio. Based on our series, the typical appearance of a gemistocytic astrocytoma is a large, heterogeneous mass most commonly supratentorial and lobar. Regions of cyst formation, partial signal suppression on FLAIR images and contrast enhancement are all common features. Additionally, contrary to previous literature that describes gemistocytic astrocytoma as a purely supratentorial lesion, we present two cases of gemistocytic astrocytoma involving the brainstem. The possibility of gemistocytic astrocytoma should be considered in patients presenting with large heterogeneous tumours that have regions of cyst formation, partial FLAIR suppression and contrast enhancement. This may be especially useful in reconciling a lesion with high-grade MR imaging features with low-grade histopathology. An infratentorial location does not preclude the diagnosis of gemistocytic astrocytoma.

Neoadjuvant Chemotherapy for Clinical Stage II and III Thoracic Esophageal Squamous Cell Carcinoma with Curative Esophagectomy

Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal carcinoma with a poor prognosis. To improve the survival of patients with this disease, neoadjuvant chemotherapy (NAC) has been introduced. However, the survival benefits of NAC or the correlation between NAC and postoperative complications have not been well considered. In the present study, we retrospectively investigated the clinicopathological effectiveness of NAC in patients with clinical stage II and III thoracic ESCC. This retrospective study enrolled 63 patients with clinical stage II and III thoracic ESCC, who underwent resection of the thoracic esophagus and three-field lymph node dissection between January 2007 and December 2013. NAC with cisplatin plus 5-fluorouracil (5-FU) was introduced in 38 patients. NAC did not correlate with the occurrence of postoperative complications. The 5-year disease-free survival (DFS) rate of the 38 patients with NAC (41.6%) was similar to that for the 25 patients who did not receive NAC (38.1%; P = 0.784). However, we found that the DFS of 17 patients with histopathological Grade 2 and 3 tumors who received NAC (5-year DFS rate: 58.1%) was significantly higher than that of 21 patients with low histopathological grade tumors who received NAC (5-year DFS rate: 28.6%), or than that of the 25 patients who did not receive NAC (38.1%). Moreover, we found that the effectiveness of NAC assessed macroscopically did not correlate with the effectiveness of NAC assessed microscopically. These findings may indicate that preoperative estimation of NAC effectiveness is important in avoiding unnecessary adverse drug effects caused by NAC, and in prolonging the survival of patients with thoracic ESCC. * Corresponding author.

Human papillomavirus, p16INK4A, and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina

Background:This study aimed to determine human papillomavirus (HPV) status and to investigate p16INK4A and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).Methods:The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (⩽2 years) and long-term (⩾8 years) PCV survivors. p16INK4A and Ki-67 expression was evaluated by immunohistochemistry.Results:Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16INK4A expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.Conclusion:High p16INK4A expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16INK4A and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16INK4A expression as a marker for HPV positivity, but this has to be further elucidated.

Liver Resections of Isolated Liver Metastasis in Breast Cancer: Results and Possible Prognostic Factors

Background. Breast cancer liver metastasis is a hematogenous spread of the primary tumour. It can, however, be the expression of an isolated recurrence. Surgical resection is often possible but controversial. Methods. We report on 29 female patients treated operatively due to isolated breast cancer liver metastasis over a period of six years. Prior to surgery all metastases appeared resectable. Liver metastasis had been diagnosed 55 (median, range 1–177) months after primary surgery. Results. Complete resection of the metastases was performed in 21 cases. The intraoperative staging did not confirm the preoperative radiological findings in 14 cases, which did not generally lead to inoperability. One-year survival rate was 86% in resected patients and 37.5% in nonresected patients. Significant prognostic factors were R0 resection, low T- and N-stages as well as a low-grade histopathology of the primary tumour, lower number of liver metastases, and a longer time interval between primary surgery and the occurrence of liver metastasis. Conclusions. Complete resection of metastases was possible in three-quarters of the patients. Some of the studied factors showed a prognostic value and therefore might influence indication for resection in the future.

Epithelial lacrimal gland tumors: A comprehensive clinicopathologic review of 26 lesions with radiologic correlation

AimTo study the prevalence, clinicopathological and radiological correlations of epithelial lacrimal gland tumors and compare these with similar published literature. The study was also designed to look at the natural history of benign mixed tumors (BMT) in regard to recurrence and malignant degeneration. MethodsThis was a retrospective study of all suspected epithelial tumors of the lacrimal gland surgically excised at King Khaled Eye Specialist Hospital (KKESH) for the period: 1983–2008. Exclusion criteria included structural lesions (dacryops) and inflammatory lesions. We included 26 cases of epithelial lacrimal gland tumors (from 24 patients). The histopathologic slides and the radiologic findings were reviewed. The corresponding demographic and clinical data were obtained by chart review using a data sheet. ResultsBMT accounted for 12/26 of the lesions while malignant lesions including adenoid cystic carcinoma (ACC) were more common (14/26). The mean age was 44.27years (range 12–75). Commonest clinical presentation was proptosis. Median duration of symptoms in the BMT cases was 30months and 7months in the ACC group. The 12 BMT cases were primary in 9 and recurrent in 3 patients. The 11 ACC cases showed mostly cribriform pattern and low histopathologic grade. We had 2 cases of malignant mixed tumor (MMT) one of which arising in a recurrent tumor. One case of primary mucoepidermoid carcinoma with histopathologic grade 2 was noted. Radiologically, a well-defined appearance with bone remodeling was observed in BMT in contrast to invasive appearance with destruction in malignant lesions. ConclusionOur series information indicated a different distribution of benign and malignant epithelial lesions with a slightly higher rate of malignancy. BMT was the commonest benign tumor where recurrence was a squeal of incomplete surgical excision. ACC was the commonest malignant tumor with shorter duration of symptoms and radiologic evidence of invasiveness that correlated with the histopathologic features.