scholarly journals Immunocytochemical expression of Ki-67/p16 in normal, atypical, and neoplastic cells in urine cytology using BD SurePath™ as preparation method

CytoJournal ◽  
2019 ◽  
Vol 16 ◽  
pp. 26 ◽  
Author(s):  
Kirsten Margrethe Østbye ◽  
Mette Kristin Pedersen ◽  
Torill Sauer

Objective: The objective of this study was to investigate the expression of Ki-67/p16 in urothelial cells in cytological material. Materials and Methods: There were 142 urines including normal controls, anonymous rest urine, controls after treatment for urothelial carcinoma (UC) and newly diagnosed UC. Immunocytochemistry for ki-67/p16 dual staining kit was performed on all specimens. Results: Eight high-grade UC and six anonymous specimens showed dual positivity. None of the low-grade UC or the control specimens after treated UC showed dual staining. Fifteen of 84 (17.8%) symptomatic cases were negative for both markers, and 59/84 (70.2%) showed positivity for both but not dual staining. Twenty-seven of 84 cases were positive for either Ki-67 (n = 22) or p16 (n = 5). Normal controls and benign specimens were negative for p16. Conclusions: Co-expression of p16/Ki-67 in the same cells was found in 16.6% of the cases. All were high grade, and co-expression seems to have limited practical impact as an additional marker in urine cytology. Any positivity for p16 alone strongly indicates malignancy. Negative p16 accompanied by a positive Ki-67 rate at 5% or more could be considered as an additional marker for further clinical follow-up. Both markers, co-expressed and separate, can give additional information in follow-up patients after treatment for UC.

Author(s):  
Laurențiu Pirtea ◽  
Cristina Secosan ◽  
Madalin Margan ◽  
Lavinia Moleriu ◽  
Oana Balint ◽  
...  

Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunohistochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred to biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged <30 years compared to patients >30 years old (p < 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and <30 years old, prior to the referral to colposcopy and biopsy.


2022 ◽  
pp. 1-8
Author(s):  
Bantita Phruttinarakorn ◽  
Sirithep Plumworasawat ◽  
Jitchai Kayankarnnavee ◽  
Jirasit Lualon ◽  
Atcharaporn Pongtippan

<b><i>Introduction:</i></b> Urothelial carcinoma is one of the most common human cancers, both in Thailand and worldwide. Urine cytology is a screening tool used to detect urothelial carcinoma. The Paris System for Reporting Urinary Cytology (TPSRUC) was first published in 2016 to standardize the procedures, reporting, and management of urothelial carcinoma. Diagnostic categories include negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUCs), suspicious for HGUC (SHGUC), HGUC, low-grade urothelial neoplasm, and other malignancies. <b><i>Material and Methods:</i></b> In a retrospective review, urine cytology specimens from 2016 to 2019 were reevaluated using the TPSRUC. The risk of high-grade malignant neoplasm (ROHM) for each diagnostic category was calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of prediction of high-grade malignant neoplasms were evaluated for cases with histological follow-up specimens. <b><i>Results:</i></b> In total, 2,178 urine cytology specimens were evaluated, of which 456 cases had follow-up histological specimens. The ROHM in each diagnostic category was as follows: NHGUC, 17.4%; AUC, 49.9%; SHGUC, 81.2%; HGUC, 91.3%; and other malignant neoplasms, 87.5%. The sensitivity, specificity, PPV, NPV, and accuracy for high-grade malignant neoplasm prediction were 63%, 92.8%, 89%, 73.1%, and 78.5% when AUC was included as malignant in the comparison and 82.6%, 74.7%, 75.1%, 82.3%, and 78.5% when AUC was not considered malignant. <b><i>Conclusions:</i></b> TPSRUC provides reliable results that are reproducible by different interpreters and is a helpful tool for the detection of HGUC.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1497-1497 ◽  
Author(s):  
Fernando Cabanillas ◽  
Noridza Rivera ◽  
Orestes Pavia ◽  
Wandaly I. Pardo ◽  
Margarita Bruno

Abstract INTRODUCTION: The typical presentation of patients with low grade lymphoma consists of disseminated lymphadenopathy, absence of constitutional symptoms, normal LDH, low Ki-67 and PET scan with low SUVs (i.e. <14). We have identified a subset of atypical cases who present with one or more clinically aggressive features. We have named these cases clinically discordant indolent histologies (CDIH). The goal of this study is to identify these cases with CDIH in order to determine if their prognosis and clinical behavior are different from those with the typical low grade NHL presentation. METHODS: We defined CDIH as any follicular grade 1-2, grade 3-A or small lymphocytic lymphoma (SLL) who meet at least one or more of the following conditions: constitutional symptoms, unexplained LDH elevation, PET SUV >14, Ki67 >30%, unusual areas of involvement for indolent NHL (bone, pleura, CNS, soft tissue, lung), necrotic areas seen in CT scan or discrete space occupying lesions in liver or spleen. We analyzed their failure free survival (FFS), overall survival (OS), rate of transformation to a high grade histology and correlation with FLIPI-2 prognostic score. RESULTS: A total of 97 cases (86 follicular, 11 SLL) with a median follow up of 56 months were identified from our data base. Of these 97 cases, 46 met the criteria for CDIH. Figure 1 shows the FFS of cases with CDIH as contrasted with 51 without CDIH. As is evident from Figure 1, those with CDIH not only had a higher relapse rate but also showed a trend for earlier relapses (within 3 years), reminiscent of high grade NHLs. Figure 2 depicts the OS of CDIH cases which is significantly inferior. We also analyzed the risk of transformation. The rate of transformation of CDIH was 5/46 (11%) in contrast to 0/51 with non CDIH (p=.02). All episodes of transformation occurred early, between 6 to 35 months from diagnosis. In order to determine if there was an underlying lymphoma of high grade histology at diagnosis, 8 cases with CDIH underwent a second biopsy of a site suspected of harboring an aggressive NHL because of findings such as SUV of ≥14. None of the 8 cases showed evidence of a high grade NHL in the second biopsy. In nearly all (94/97=97%) treatment included rituximab in combination with chemo and 80% of these were given maintenance. Management consisted of: Treatment A (n=55)-non-doxorubicin regimens, mostly fludara or bendamustine based; Treatment B (n=19)-R-CHOP; Treatment C (n=23)-R-CHOP x 6 followed by fludara based regimen (FND) x 4. The latter was used primarily for CDIH. Of the 46 cases of CDIH, 31 were treated with a doxorubicin-rituximab combination (either Treatment B or C). Their OS at 8 years was 98 % vs 62% for those who received a non- doxorubicin regimen (Treatment A), p=0.014. Of 40 cases without CDIH who received Treatment A, only 1 has relapsed. FLIPI-2 prognostic score correlated poorly with CDIH: of 23 with high risk score, 12 had CDIH and of 7 with low risk, 3 were CDIH. CONCLUSIONS: 1-Cases with CDIH have less favorable OS, FFS, and higher rate of transformation to a higher grade histology. 2-In spite of the fact that CDIH histologically is identical to an indolent NHL, it functionally behaves as an aggressive NHL with frequent early relapses. 3-FLIPI-2 prognostic score correlates poorly with CDIH. This is not surprising since FLIPI-2 score doesn't include B symptoms and LDH. 4-Confirmatory biopsies to rule out co-existing high grade NHL at diagnosis are not useful or recommended. 5-Those without CDIH do very well when treated with a non-doxorubicin regimen such as a fludarabine-rituximab containing combination while CDIH cases appear to fare better when treated with a doxorubicin-rituximab containing regimen. These conclusions have to be interpreted in light of the retrospective nature of the study. Disclosures No relevant conflicts of interest to declare.


2016 ◽  
Author(s):  
Dharma Ram

Introduction: Uterine sarcoma accounts for nearly 3% of all uterine malignancies. They have 4 major pathology includes endometrial stromal sarcoma high grade, ESS low grade, uterine leiomyosarcoma (uLMS) and undifferentiated uterine sarcoma (UUS). Recent WHO classification 2014, recognizes low grade ESS and high grade ESS as distinct entity. They differ from endometrial carcinoma in their aggressive nature and poor prognosis. We review our database and found total 44 eligible patient treated at our institute. Materials and Methods: Its retrospective analysis of computer based database of our institute from January 2009 to December 2015. We analyzed demographic, pathological, treatment and survival data. Results: Total 44 patient treated for uterine sarcoma at our institute. Among these 16 were operated at our institute during study period. Here we reporting results of operated patients at our institute. The histological diagnosis LMS (5/16), ESS-L (4/16), MMMT (3/16), UUS (3/16) and ESS-H (1/16). Stage distribution was stage I, (6/16) stage II, (5/16) stage III, (3/16) stage IV, (0/16) and unknown stage (2/16). Two patients underwent completion surgery for outside myomectomy. The adjuvant treatment was CT in 3/16, CT with RT in 7/16, HT in 4/16 and one lost to follow up with one was put on observation. Median follow up is 30 month with 14 patients alive and one lost to follow up. At last follow up 4 patients alive with metastatic disease and 10 patients alive with no evidence of disease. Conclusion: Uterine sarcoma are uncommon disease with


2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.


2003 ◽  
Vol 48 (2) ◽  
pp. 43-45 ◽  
Author(s):  
E F Shen ◽  
S Gladstone ◽  
G Milne ◽  
S Paterson-Brown ◽  
I D Penman

Management of columnar lined oesophagus (CLO; Barrett s oesophagus) is controversial. We prospectively audited surveillance practices in Scotland and prospectively assessed the impact of introducing local guidelines for Barrett s surveillance in Edinburgh. Most respondents were gastroenterologists. The majority take random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80 patients underwent surveillance. The guideline protocol was not followed in 30 (37.5%) patients. Follow up of patients without dysplasia generally conformed to the guidelines. Follow up of patients with low grade dysplasia was highly variable while management of those with high grade dysplasia followed the guidelines. Overall we found a wide variability in the management and surveillance of CLO. Early experience suggests that implementation of guidelines is helpful but there is still variation in practice.


2017 ◽  
Vol 45 (5) ◽  
pp. 1095-1101 ◽  
Author(s):  
Bum-Sik Lee ◽  
Seong-Il Bin ◽  
Jong-Min Kim ◽  
Won-Kyeong Kim ◽  
Jun Weon Choi

Background: Clinical outcomes after meniscal allograft transplantation (MAT) in arthritic knees are unclear, and objective estimates of graft survival according to the articular cartilage status have not been performed. Hypothesis: MAT should provide clinical benefits in knees with high-grade cartilage damage, but their graft survivorship should be inferior to that in knees with low-grade chondral degeneration after MAT. Study Design: Cohort study; Level of evidence, 3. Methods: The records of 222 consecutive patients who underwent primary MAT were reviewed to compare clinical outcomes and graft survivorship. The patients were grouped according to the degree and location of articular cartilage degeneration: low-grade chondral lesions (International Cartilage Repair Society [ICRS] grade ≤2) on both the femoral and tibial sides (ideal indication), high-grade lesions (ICRS grade 3 or 4) on either the femoral or tibial side (relative indication), and high-grade lesions on both sides (salvage indication). Kaplan-Meier survival analysis with the log-rank test was performed to compare the clinical survival rates and graft survival rates between the groups. A Lysholm score of <65 was considered a clinical failure, and graft failure was defined as a meniscal tear or meniscectomy of greater than one-third of the allograft, objectively evaluated by magnetic resonance imaging (MRI) and second-look arthroscopic surgery. Results: The mean (±SD) Lysholm score significantly improved from 63.1 ± 15.1 preoperatively to 85.1 ± 14.3 at the latest follow-up of a mean 44.6 ± 19.7 months ( P < .001). However, the postoperative scores were not significantly different between the 3 groups (85.7 ± 14.2 for ideal indication, 84.7 ± 17.0 for relative indication, and 84.7 ± 14.2 for salvage indication; P = .877). On MRI at the latest follow-up of a mean 23.0 ± 19.9 months and second-look arthroscopic surgery of a mean 19.3 ± 20.7 months, there were 25 (11.3%) failed MAT procedures (4 medial, 21 lateral); of these, 5 lateral MAT procedures (2.3%) went on to allograft removal. Clinical survival rates were not significantly different between the groups ( P = .256). However, on objective evaluation, the estimated cumulative graft survival rate at 5 years in the salvage indication group (62.2% [95% CI, 41.6-82.8]) was significantly lower than that in the other 2 groups (ideal indication: 93.8% [95% CI, 88.5-99.1]; relative indication: 90.9% [95% CI, 81.1-100.0]) ( P = .006). Conclusion: Our findings showed that MAT was an effective symptomatic treatment in knees with advanced bipolar chondral lesions. However, better graft survival can be expected when articular cartilage is intact or if chondral damage is limited to a unipolar lesion. MAT should be considered before the progression of chondral damage to a bipolar lesion for better graft survivorship and should be performed cautiously in arthritic knees.


Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Roberto Chiarle ◽  
Leo M. Budel ◽  
Jeffrey Skolnik ◽  
Glauco Frizzera ◽  
Marco Chilosi ◽  
...  

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)


2013 ◽  
Vol 137 (10) ◽  
pp. 1337-1341 ◽  
Author(s):  
Melissa L. Stanton ◽  
Li Xiao ◽  
Bogdan A. Czerniak ◽  
Charles C. Guo

Context.—Urothelial tumors are rare in young patients. Because of their rarity, the natural history of the disease in young patients remains poorly understood. Objective.—To understand the pathologic and clinical features of urothelial tumors of the urinary bladder in young patients. Design.—We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution and analyzed the tumors' pathologic features and the patients' clinical outcomes. Results.—All patients were 30 years or younger, with a mean age of 23.5 years (range, 4–30). Thirty-eight patients (64%) were male, and 21 (36%) were female. Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%), including papillary urothelial neoplasms of low malignant potential (7 of 49; 14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade papillary urothelial carcinomas (4 of 49; 8%). Only a few (n = 10) of the urothelial tumors were invasive, invading the lamina propria (n = 5; 50%), muscularis propria (n = 4; 40%), or perivesical soft tissue (n = 1; 10%). Clinical follow-up information was available for 41 patients (69%), with a mean follow-up time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors, only 1 patient (3%) later developed an invasive urothelial carcinoma and died of the disease, and 30 of these patients (97%) were alive at the end of follow-up, although 10 (32%) had local tumor recurrences. In the 10 patients with invasive urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%) were alive with metastases (the other 2 [20%] were alive with no recurrence). Conclusion.—Urothelial tumors in young patients are mostly noninvasive, papillary carcinomas and have an excellent prognosis; however, a small subset of patients may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.


2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.


Sign in / Sign up

Export Citation Format

Share Document