Histopathological Differentiation Grade Research Articles

Cutaneous Squamous Cell Carcinoma: Clinico-Dermoscopic and Histological Correlation: About 72 Cases.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, accounting for 20% of malignant skin tumors. Dermoscopy is a very useful tool for diagnosing cSCC, and its findings are confirmed through histopathological studies. to describe the different dermoscopic structures of invasive cSCC and investigate their association with the clinical form and histopathological grade of differentiation. We conducted a cross-sectional study, collecting all patients diagnosed with squamous cell carcinoma over a period of 5 years. The study population was divided into two groups based on histological differentiation (well-differentiated and non-well-differentiated) and clinical form ( nodulo-ulcerative and nodular). Various dermoscopic parameters were compared between these groups. Out of 72 invasive cSCC, 81.9% were well-differentiated, while 18.1% were non-well-differentiated. The clinical form of cSCC was nodulo-ulcerative in 83.3% of cases and nodular in 16.7%. Well-differentiated tumors showed dotted, glomerular and hairpin vessels, along with a predominant white pattern characterized by centrally distributed keratin as well as white circles, and whitish perivascular halo (P < 0.05). The distribution of these white structures was radial in nodulo-ulcerarive lesions, whereas in nodular lesions, their distribution, as well as that of keratin, was more diffuse (P < 0.05). Non-well-differentiated tumors showed a combined white-red pattern with the predominance of arborizing vessels (P < 0.05). Our results show the reliability of dermoscopy as a tool for distinguishing between well- and poorly differentiated cSCC. This distinction is characterized by an increase in predominantly arborizing vessels and a corresponding decrease in white structures as the tumor progresses from a well-differentiated to a poorly differentiated state. Additionally, the nodulo-ulcerative form exhibits a central distribution of keratin, while the nodular form displays a diffuse distribution.

Pancreatic Ductal Adenocarcinoma: Machine Learning-Based Quantitative Computed Tomography Texture Analysis For Prediction Of Histopathological Grade.

PurposeTo assess the performance of combining computed tomography (CT) texture analysis with machine learning for discriminating different histopathological grades of pancreatic ductal adenocarcinoma (PDAC).MethodsFrom July 2012 to August 2017, this retrospective study comprised 56 patients with confirmed histopathological PDAC (32 men, 24 women, mean age 64.04±7.82 years) who had undergone preoperative contrast-enhanced CT imaging within 1 month before surgery. Two radiologists blinded to the histopathological outcome independently segmented lesions for quantitative texture analysis. Histogram features, co-occurrence, and run-length texture were calculated. A support-vector machine was constructed to predict the pathological grade of PDAC based on preoperative texture features.ResultsPathological analysis confirmed 37 low-grade PDAC (five well-differentiated/grade I and 32 moderately differentiated/grade II) and 19 high-grade PDAC (19 poorly differentiated/grade III) tumors. There were no significant differences in clinical or biological characteristics between patients with high-grade and low-grade tumors (P>0.05). There were significant differences between low-grade PDAC and high-grade PDAC on nine histogram features, seven run-length features, and two co-occurrence features. Cluster shade was the most important predictor (sensitivity 0.315). Using these texture features, the support-vector machine achieved 86% accuracy, 78% sensitivity, 95% and specificity.ConclusionMachine learning–based CT texture analysis accurately predicted histopathological differentiation grade of PDAC based on preoperative texture features, leading to maximization patient survival and achievement of personalized precision treatment.

Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade.

The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and clinical significance of annexin A9 (ANXA9) and A10 (ANXA10) in head and neck squamous cell carcinomas (HNSCC). ANXA9 and ANXA10 expression was evaluated in a large cohort of 372 surgically treated HPV-negative HNSCC patients and correlated with the clinicopathologic parameters and disease outcomes. Down-regulation of ANXA9 expression was found in 42% of HNSCC tissue samples, compared to normal epithelia. ANXA9 expression in tumors was significantly associated with oropharyngeal location and histological differentiation grade (p < 0.001). In marked contrast, ANXA10 expression was absent in normal epithelium, but variably detected in the cytoplasm of cancer cells. Positive ANXA10 expression was found in 64% of tumors, and was significantly associated with differentiation grade (p < 0.001), being also more frequent in oropharyngeal tumors (p = 0.019). These results reveal that the expression of both ANXA9 and ANXA10 is frequently altered in HNSCC and associated to the tumor differentiation grade, suggesting that they could be implicated in the pathogenesis of these cancers.

Differentiation grade for extrahepatic bile duct adenocarcinoma: Assessed by diffusion-weighted imaging at 3.0-T MR

Purpose—To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR. Methods—Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed. Results—In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P=0.426) and SIR-LH value (P=0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506×10−3mm2/s, 1.275×10−3mm2/s and 1.154×10−3mm2/s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x2=51.220, P=0.000). The ADC value <1.184×10−3mm2/s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316×10−3mm2/s can forecast the well-differentiated EBDA with a sensitivity of 100% and a specificity of 84.78%. Conclusions—The histopathological differentiation grade of EBDA can be detected non-invasively using DWI at 3.0-T MR.

Expression of Molecular Differentiation Markers Does Not Correlate with Histological Differentiation Grade in Intrahepatic Cholangiocarcinoma.

The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1β), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria.

Correlation between 18F-fluorodeoxyglucose positron emission tomography and pathologic differentiation in pancreatic cancer

The histopathological grade of differentiation is one of the significant prognostic factors in pancreatic adenocarcinoma. Especially in the patients with unresectable pancreatic cancer, it is important to obtain the prognostic information non-invasively to avoid unnecessary invasive procedure. The aim of the study was to correlate (18)F-fluorodeoxyglucose (FDG) uptake with pathologic grade of pancreatic cancer, furthermore, to evaluate prognostic value of standardized uptake value (SUV). FDG-PET scans of 102 patients with histologically proven pancreas adenocarcinoma were retrospectively reviewed. SUV of the primary tumor was calculated for quantification analysis. Pathological differentiation was graded into well-, moderately, and poorly differentiated groups. One-way analysis of variance is performed to test the correlation of the SUV and histopathologic grades. Patients were assigned into 3 categorical groups, using SUV cut-offs of 4 and 7, respectively. Survival functions of different histologic grade and assigned groups according to SUV were estimated by Kaplan-Meier estimator and compared by log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model. There was a significant correlation of SUVs and pathologic grades (F=4.97, p<0.01). The mean SUV of well-, moderately and poorly differentiated groups was 4.93, 6.47 and 7.29, respectively. Tumor size, AJCC stage and treatment method were significantly related to the degree of FDG uptakes. SUV also shows a significant correlation with survival (p<0.01), with better prognosis in lower SUV group. In multivariate analysis, the treatment method was the most strongly independent predictor (p<0.01), followed by age (p=0.04) and tumor size (p=0.06). In moderately differentiated group, higher SUV showed significantly worse survival (p=0.02). SUV is related with histologic grade and might be competitive predictor for patients' survival. Specifically, the prognosis of the patients with moderately differentiated pancreas adenocarcinoma could be stratified according to SUV.

The up-regulation expression of APRIL is a marker of glottic malignant disease

A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) family. Recent studies have implied that APRIL is closely related to solid tumors and hematological tumors, indicating that APRIL could be a potential marker to diagnose glottic malignant disease. The purpose of this study was to investigate the difference of the APRIL mRNA and protein expression in glottic malignant disease, corresponding adjacent non-neoplastic tissues and glottic benign lesion, and detect the influence of different clinical parameter in glottic carcinoma. The APRIL mRNA expression in the glottic carcinoma, corresponding adjacent non-neoplastic tissues and glottic polypus tissue samples from patients was detected by qRT-PCR. Moreover, we studied the APRIL protein expression in pathological sections of other patients with glottic carcinoma or glottic polypus using immunohistochemistry. All the patients with different clinical parameter underwent surgery. Using qRT-PCR, we revealed an up-regulation of APRIL mRNA expression in glottic carcinoma as compared to glottic polypus and corresponding adjacent non-neoplastic tissues, but no significant difference with T stages, histopathological differentiation grade or lymph node metastasis in glottic carcinoma. The result of the immunohistochemistry was the same, with no influence of different clinical parameter in glottic carcinoma. These results strongly suggest that APRIL could be a potential diagnosed marker to distinguish glottic malignant disease from glottic benign lesion, and it may play an important role in the development of glottic malignant disease.

Expression of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) in Human Non-small Cell Lung Carcinoma: Correlation with Clinicopathological Parameters, Proliferation and Apoptosis Related Molecules and Patients’ Survival

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has currently been considered as molecular target for the treatment of human metabolic disorders. PPAR-γ has also been implicated in the pathogenesis and progression of several types of cancer, being associated with cell differentiation, growth and apoptosis. The present study aimed to evaluate the clinical significance of PPAR-γ expression in non-small cell lung carcinoma (NSCLC). PPAR-γ protein expression was assessed immunohistochemically in tumoral samples of 67 NSCLC patients and was statistically analyzed in relation to clinicopathological parameters, proliferation and apoptosis related molecules and patients' survival. Positive PPAR-γ expression was prominent in 30 (45 %) out of 67 NSCLC cases. PPAR-γ positivity was more frequently observed in squamous cell lung carcinoma cases compared to lung adenocarcinoma ones (p = 0.048). PPAR-γ positivity was significantly associated with bcl-2 positivity (p = 0.016) and borderline with c-myc positivity (p = 0.052), whereas non associations with grade of differentiation, TNM stage, Ki-67, p53, bax proteins' expression and patients' survival were noted. In the subgroup of squamous cell lung carcinoma cases, PPAR-γ positivity was significantly associated with tumor size (p = 0.038), while in lung adenocarcinoma ones with histopathological grade of differentiation (p = 0.026). The present study supported evidence for possible participation of PPAR-γ in the biological mechanisms underlying the carcinogenic evolution of the lung. Although the survival prediction using PPAR-γ expression as a marker seems uncertain, the observed correlation with apoptosis related proteins reinforces the potential utility of PPAR-γ ligands as cell cycle modulators in future therapeutic approaches in lung cancer.

Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival

Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease-free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty-seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis.

IGF-IR in patients with advanced colorectal cancer in correlation with certain clinico-morphological factors: Initial report.

The insulin-like growth factor (IGF) system comprises two types of peptides (IGF-I and IGF-II), two types of receptors (IGF-IR and IGF-IIR) and six IGF-binding proteins (BP). This system is mainly responsible for the growth and division of cells in the body, regulation of the cell cycle and prevention of apoptosis. The expression of IGF-IR was assessed in the cells of resected primary colorectal tumours in 88 patients (age, 36-87 years; mean 64.78; males, 48 and females, 40) treated surgically at the Second Department of General and Gastroenterological Surgery, Medical University of Bialystok, Poland, in relation to various clinico-morphological factors. The post-operative material was analysed to find the histological type, location of lesions, lymph node involvement staging, distant metastases (pTNM classification), staging in Dukes' classification and the histopathological differentiation grade. The expression of IGF-IR in colorectal cancer cells was assessed using an immunohistochemical method. The findings were subjected to statistical analysis (Chi-square test, multivariation test and Mann-Whitney U test). A positive IGF-IR expression (in at least 10% of cancer cells) was observed in 44 patients. The mean immunoreactive cell count for IGF-IR in all of the tumours studied was 30.79%. The current study showed no correlation of IGF-IR expression in colorectal cancer cells with characteristics such as age and gender of patients, tumour location, type, histological differentiation or histopathological advancement. Immunohistological determination of IGF-IR expression in advanced colorectal cancer cells revealed controversial scores. Evaluation should be confirmed by using other methods and enhanced to include adenomas and early colorectal cancers.

Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival

Histone deacetylases (HDACs) have been associated with tumor development and progression in several types of human malignancy and HDAC inhibitors are currently being explored as anti-cancer agents in clinical trials. The aim of the present study was to evaluate the clinical significance of HDAC-1 and -2 protein expression in mobile tongue squamous cell carcinoma (SCC). HDAC-1 and -2 protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. HDAC-1 overexpression was significantly associated with younger patients' age (P = 0.0381) and male gender (P = 0.0345), poor histopathological grade of differentiation (P = 0.0236) and the presence of lymph node metastases (P = 0.0104). Intense HDAC-1 staining intensity was significantly associated with male gender (P = 0.0127), increased stromal infiltration reaction (P = 0.0125) and well-defined shape of tumor invasion (P = 0.0396). HDAC-2 overexpression did not show significant correlations with any clinicopathological parameters, whereas intense HDAC-2 staining intensity was significantly associated with the presence of muscular invasion (P = 0.0466) and advanced depth of invasion (P = 0.0251). Mobile tongue SCC patients with HDAC-1 overexpression presented shorter overall and disease-free survival compared to those with no evidence of HDAC-1 overexpression (log-rank test, P = 0.0651 and 0.0247, respectively). The present study supported evidence that HDACs may participate in the formation and progression of mobile tongue SCC, reinforcing their possible use as biomarkers as also the therapeutic utility of HDAC inhibitors in mobile tongue SCC chemoprevention and treatment.

DNA amplification and expression of FADD in oral squamous cell carcinoma

The Fas-associated death domain-containing protein, FADD, is an adaptor for relaying apoptotic signals. However, recent studies have shown that FADD also plays an important role in the growth and regulation of the cell cycle. The purpose of this study was to elucidate the role of FADD in oral squamous cell carcinoma (SCC). The DNA amplification of FADD from 30 samples of tongue SCC was analyzed using real-time PCR and the protein expression of FADD from 60 samples of tongue SCC was analyzed using immunohistochemistry. The DNA amplifications of FADD were observed in 13 cases (44.3%) and were significantly correlated with the histopathological differentiation grade of SCCs (P = 0.009). FADD expression levels compared with the matched adjacent epithelium increased significantly (P = 0.000). Additionally, the positive expressions of FADD were significantly correlated with lymph node metastasis of SCCs (P = 0.029) and the 5-year disease-specific survival rates (P = 0.049). A positive association between FADD expression level and the histopathological differentiation grade was found to be limited to T1 SCCs (P = 0.019). DNA amplification was moderately correlated (correlation coefficient = 0.406, P = 0.026) with expression of FADD in 30 samples of tongue SCC. In tongue SCCs, the expression of FADD was higher when compared with that of adjacent areas, which might be determined via genomic amplification in 11q13.3. Thus, SCC cells with the expression of FADD are possibly more likely to become metastatic and to worsen survival rates.

Loss of Hugl-1 Expression Associates With Lymph Node Metastasis in Endometrial Cancer

Mutation of neoplastic tumor suppressor genes, scribble, discs large, and lethal giant larvae (lgl), causes disruption of cell polarity and overproliferation of Drosophila epithelial cells and neuroblasts. Reduced expression of human homologue of lgl, Hugl-1, has been reported to be involved in development and progression of human colon cancer and malignant melanoma. To explore the association between Hugl-1 expression and clinical character in endometrial cancer, we examined the expression of Hugl-1 in primary endometrial cancer tissues. The expression of Hugl-1 mRNA in 86 primary endometrial cancer tissues was examined using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). All samples were categorized into two groups: Hugl-1 positive and Hugl-1 negative. Clinical data of each group were analyzed by Fisher's exact probability test and survival rates of each group were compared by Kaplan-Meier method and Log-rank test. Loss of Hugl-1 expression had correlation with the higher incidence of lymph node metastasis, but not to the patient's age at onset, distant metastasis, clinical stage, lymph or venous vessel invasion, or histopathological grade of differentiation. The Hugl-1-positive group had poorer prognosis compared with the Hugl-1-negative group. These results indicate that loss of Hugl-1 expression in endometrial cancer may contribute to lymph node metastasis and it can be a factor of poor prognosis.

P.1.044 WAY-181187: neurochemical profile of a novel and selective 5-HT6 receptor agonist

To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR.Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed.—In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P = 0.426) and SIR-LH value (P = 0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506 × 10−3 mm2/s, 1.275 × 10−3 mm2/s and 1.154 × 10−3 mm2/s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x2 = 51.220, P = 0.000). The ADC value <1.184 × 10−3 mm2/s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316 × 10−3 mm2/ s can forecast the well-differentiated EBDA with a sensitivity of 100% and a specificity of 84.78%.The histopathological differentiation grade of EBDA can be detected non-invasively using DWI at 3.0-T MR.

Hepatocellular carcinoma in liver transplant era: a clinicopathologic analysis

Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and the prognosis is usually poor. Today, liver transplantation (LT) is a radical but frequently curative treatment modality for HCC. In selected patients, it cures HCC and the underlying cirrhosis at the same time. The present clinicopathological study examined the importance of tumor characteristics for their effects on recurrence and survival rates after LT for HCC. Forty-two native hepatectomy specimens among 250 consecutive orthotopic liver transplantations contained HCC. Patients were predominantly men (30 men, 12 women), ranging in age from 1 to 61 years (median 51). While 20 patients received cadaveric organs, 22 were transplanted from living donors. In 14 patients (33%) HCC presented as a solitary nodule, 5 (12%) as two nodules; 2 (5%) as three nodules; and 21 patients (50%) as more than three nodules. The maximal diameter of the largest tumor not larger than 3 cm in 28 patients (66%), exceeding this size in 14 patients (34%). There was a significant correlation between nodule number and tumor size ( r = 0.36, P = 0.05). While 23 patients had no sign of vascular involvement, 17 tumors showed microscopic invasion and two large vessel involvement. There was a positive correlation between vascular invasion and nodule number ( r = 0.41, P = 0.05). The histopathological grade of differentiation of the tumors was assessed as “well” in seven patients (14%), moderate in 28 (72%), and poor in 7 (14%). The differentiation was significantly poorer when vascular invasion was observed ( r = 0.43, P = .01). According to the TNM classification, 11 patients (26%) were stage I, 6 (14%) stage II, 13 (31%) stage III, and 12 (29%) stage IV. After a median follow-up of 10 months (1–50 months), the overall mortality was 18% ( n = 8). Patient survival at 6 month, 1, and 4 years was 88%, 80%, and 60%, respectively. The outcome was significantly poorer for TNM stage IV versus stage I,II, and III tumors to ( P = .02). Tumor recurred in three patients at 4,6, and 50 months after liver transplantation. The sites of recurrence were bone, lung, and adrenal glands. In conclusion, liver transplantation represents a safe and feasible treatment for hepatocellular carcinoma with excellent outcomes compared with other treatment modalities. Liver transplantation offers excellent survival rates and chance for cure in stages I, II, and III hepatocellular carcinoma in cirrhotic patients.

Relationship between AgNOR proteins, Ki-67 antigen, p53 immunophenotype and differentiation markers in archival breast carcinomas.

The present study investigated (i) the relationship between standardised morphometric AgNOR parameters (argyrophilic nucleolar organiser region-associated proteins) and MIB1 growth fraction, and (ii) their correlation with immunohistochemical p53, sex steroid receptor status and histopathological differentiation grade in serial paraffin sections from 39 breast carcinomas. Ten sections were double-stained for AgNOR/MIB1. AgNOR parameters correlated significantly with MIB1 growth fraction and p53 protein expression. Significant inverse correlation was found between proliferation markers and oestrogen/progesterone receptor status and histopathological grade. AgNOR expression was significantly higher in cycling (MIB1 positive) tumour cells, than in resting (MIB1 negative) ones, however with exceptions. We conclude, that standardised AgNOR parameters correlate with markers of increased malignant potential in breast carcinomas. However, AgNORs seem to reflect proliferation independent cellular and nucleolar activity of tumour cells, as well. We recommend the use of standardised AgNOR analysis for obtaining sound results in routine paraffin sections.

Frequent allelic deletion at a novel locus on chromosome 5 in human lung cancer : Wieland I, Bohm M. Institut fur Zellbiologie, Universitatsklinikum Essen, Virchowstrasse 173, 45122 Essen. Cancer Res 1994;54:1772-4

Frequent allelic deletions in tumor cells are indicative of the inactivation of tumor suppressor genes. Recently, we isolated the single-copy sequence del-27 (I. Wieland, M. Böhm, and S. Bogatz, Proc. Natl. Acad. Sci. USA, 89: 9705-9709, 1992). Here we show that del-27 detects a restriction fragment length polymorphism that allows examination for loss of heterozygosity (LOH) in tumor specimens. LOH at the del-27 locus occurred in 57% (4 of 7) of the informative lung carcinomas independent of the histopathological differentiation grade. LOH for exon 11 of the APC gene occurred in 71% (5 of 7) of the informative cases but was not associated with LOH at the del-27 locus. The del-27 sequence was localized to chromosome 5p13-5q14, proximal to the MCC/APC region, using a somatic cell hybrid panel. Together with our previous finding that del-27 is deleted homozygously in a lung carcinoma cell line, these results suggest that del-27 is linked closely to a novel putative tumor suppressor gene.