Yulia Strenov

Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

Expression of Ki‐67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki‐67 proliferation index (PI) in non‐Hodgkins lymphoma. Ki‐67 was assayed immunohistochemically in tissue samples of 319 patients with newly‐diagnosed non‐Hodgkins lymphoma. In 268 patients, the Ki‐67 PI was correlated with clinical course and outcome. The mean Ki‐67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse large B‐cell lymphoma (n = 141), a Ki‐67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three‐year survival was 75% ± 5.6% in patients with a low Ki‐67 index compared with 55.9% ± 6% in patients with a high index (P = 0.015). In patients with a low IPI (≤2), 3‐year survival was 94% ± 4% in those with a Ki‐67 index ≤70% and 64% ± 8.1% in those with a higher index (P = 0.002); in patients with bulky disease (>10 cm), the corresponding 3‐year survival by Ki‐67 index was 100% and 25% ± 12% (P = 0.012). Our results suggest that the mean Ki‐67 PI differs by type of lymphoma. A cut‐off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B‐cell lymphoma, a cut‐off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 2009.

MicroRNA expression differentiates between primary lung tumors and metastases to the lung.

For surgical pathologists, distinguishing whether a pulmonary neoplasm is primary or metastatic can be challenging, and current biomarkers do not always aid lung tumor classification. The tissue-associated expression of microRNA likely explains the remarkable finding that many tumors can be classified based solely on their microRNA expression signature. Here we show that microRNAs can serve as biomarkers for lung tumor classification. Using microRNA microarray data generated from 76 formalin-fixed, paraffin-embedded (FFPE) samples of either primary lung cancer or metastatic tumors to the lung, we have identified a set of microRNAs expressed differentially between these two groups. This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors. The differential expression of this set of microRNAs was confirmed using qRT-PCR on a set of 54 samples. In light of our data, microRNA expression should be considered as a potential clinical biomarker for surgical pathologists faced with discerning the tumor type of an inscrutable lung neoplasm.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and the associated lung neuroendocrine tumors: clinical experience with a rare entity.

Normal adult lungs contain pulmonary neuroendocrine cells (PNECs). PNEC hyperplasia may be either reactive or idiopathic, and the idiopathic type is defined as diffuse idiopathic PNEC hyperplasia (DIPNECH). It is believed that DIPNECH is a neuroendocrine proliferative process associated with carcinoid tumors. The available data regarding this rare condition are very limited. The objective of the current study was to describe the clinical, radiologic, and pathologic characteristics of patients with DIPNECH and the effect of various therapeutic modalities on patient well being.

Differentiated Thyroid Cancer Is Associated With Less Aggressive Disease and Better Outcome in Patients With Coexisting Hashimotos Thyroiditis

BACKGROUND Evaluation of surgical specimens suggests that patients with Hashimoto thyroiditis (HT) have a higher prevalence of differentiated thyroid cancer. Although patients with HT are reported to present with earlier stage disease, there is controversy as to whether these patients have better prognosis when adjusted for histology and stage at presentation. OBJECTIVES To investigate differences between patients with differentiated thyroid cancer patients and without HT for aggressiveness of disease and clinical outcome, and the decline rate of antithyroglobulin antibodies titers over time. METHODS A retrospective study using the Rabin Medical Center Thyroid Cancer Registry. Seven hundred fifty-three patients were included and divided into 2 groups of patients with and without HT at diagnosis. Disease severity at presentation was evaluated using the entire cohort, whereas a control group matched for age, gender, histology, and stage was used to evaluate disease course and outcome. RESULTS HT was present in 14.2% (n = 107) of included patients and was associated with smaller primary tumor (17.9 vs 21.2 mm, P = .01) and less lymph node involvement (23% vs 34%, P = .02) at presentation. When matched groups were compared, patients with HT received less additional radioactive iodine (RAI) treatments (1.24 vs 1.45, P = .03) and showed lower rates of persistence at 1 year (13% vs 26%, P = .04) and higher rates of disease remission at the end of follow-up (90% vs 79%, P = .05). On multivariate analysis HT was predictive of a lower rate of lymph nodes involvement (odds ratio 0.34, 95% confidence interval 0.17-0.66) and persistent disease at the end of follow-up (odds ratio 0.48, 95% confidence interval 0.24-0.93). Antithyroglobulin antibodies slowly disappeared in most patients with no evidence of disease. CONCLUSION Our study demonstrates that HT is associated with a less aggressive form of differentiated thyroid cancer and a better long-term outcome.

Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome.

Clin. Otolaryngol. 2010, 35, 307–312

ORIGINAL ARTICLE: Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome

Clin. Otolaryngol. 2010, 35, 307–312

Pediatric Thyroid Cancer: Postoperative Classifications and Response to Initial Therapy as Prognostic Factors

CONTEXT Prognostic factors for pediatric differentiated thyroid cancer (DTC) are not well established. OBJECTIVE The objective of the study was to retrospectively compare the postoperative risk-stratification systems: American Thyroid Association (ATA) risk categories, Schneider Childrens Medical Center of Israel (SCMCI) score, and the response to initial therapy as predictors for disease outcome. PATIENTS AND METHODS Fifty-four DTC patients, median age at diagnosis 13.9 years (range 1.9-17 y), followed up for a median of 8.8 years (range 2.6-20.5 y) were stratified into prepubertal (n = 9), pubertal (n = 25), and postpubertal (n = 20) groups. All patients underwent total/near-total thyroidectomy; 48 received radioiodine therapy. The extent of DTC was evaluated by applying the ATA risk categories and the novel SCMCI score. Postoperative risk stratifications (low/intermediate/high) were determined using histopathological, laboratory, and imaging findings. Response to initial therapy (complete/acceptable/incomplete) was based on stimulated thyroglobulin and imaging results during the first 2 years of follow-up. RESULTS The risk for recurrent/persistent disease, as assessed by the postoperative ATA risk-stratification system and the SCMCI score and by the response to initial therapy, was higher in the prepubertal group (P < .001, P = .002, and P = .02, respectively). Outcome prediction by the risk-stratification systems was applicable: ATA risk categories, P = .014, R(2) = 0.247, predictive ability 80.4%; SCMCI score, P < .001, R(2) = 0.435, predictive ability 86.3%; and response to initial therapy stratification, P < .001, R(2) = 0.789, predictive ability 96.1%. The proportion of variance explained by the ATA risk categories (0.25), SCMCI score (0.44), and response to initial therapy (0.79) indicated that the latter was the most precise predictor and that the SCMCI score reflected the disease outcome better than ATA risk categories. CONCLUSIONS Our data confirm that the postoperative pediatric ATA stratification system and the novel SCMCI score are suitable for predicting the risk of recurrent/persistent disease in this population. The response to initial therapy classification performed 1-2 years after the initial therapy may be more appropriate for guiding surveillance recommendations.

Early death from papillary thyroid carcinoma

PURPOSE The natural history of papillary thyroid carcinoma (PTC) is characterized by a slow growth rate and an excellent prognosis at 20 and 30 years. However, there is a small subset of patients with poorer outcome. METHODS Twenty patients who died of PTC within 10 years of diagnosis were studied to identify prognostic indicators and biological markers of early death. Findings were statistically compared with a previous review of all patients with PTC treated in the same institute and studies in the literature. RESULTS The study group included 6 men and 14 women with a mean age of 65 years at diagnosis. Average tumor size was 3.6 cm; 16 patients had extracapsular extension. All tumor samples studied histologically stained poorly for p53, Ki67, and CD34. Regional metastases were present in half the patients, and distal metastases in all. All patients had an advanced disease stage (Tumor, Node, Metastases classification), and only 4 had a low score on the Metastases, Age, Completeness of resection, local Invasion, tumor Size risk stratification. Analysis of the findings against data in the literature for the whole population of patients with PTC, who had a considerably better survival (<8% mortality within 8-15 years vs 100% within 10 years in our sample), yielded significant differences for rates of extrathyroidal extension (P = .0001), regional metastases (P = .016), and distant metastases (P = .0001). CONCLUSION Extrathyroid extension, late regional metastases, and distant metastases may be risk factors for early death from PTC.

Early tongue carcinoma: Analysis of failure

Failure rate of surgery for early tongue carcinoma remains high. We sought to identify patterns of failure and recurrence risk factors.

Distinctive pattern of let-7 family microRNAs in aggressive carcinoma of the oral tongue in young patients

Oral cavity squamous cell carcinoma may be more aggressive at presentation and recurrence in young patients compared with older patients. Dysregulation of microRNAs (miRNAs or miRs) has been associated with the development and prognosis of oral cavity cancer. The present study investigated miRNA expression in carcinoma of the oral tongue in young patients. miRNA expression profiles were evaluated in formalin-fixed, paraffin-embedded samples of tumor and normal mucosa from 12 patients aged <30 years old with squamous cell carcinoma of the tongue. The levels of let-7f-5p, miR-30b-5p and let-7e-5p were upregulated in tumors (P<0.05). The expression of let-7f-5p was upregulated in non-aggressive tumors, while the expression of let-7e-5p was upregulated in aggressive tumors, compared with the corresponding normal tissue. Aggressive tumors had higher levels of let-7c, miR-130a-3p, miR-361-5p, miR-99a-5p, miR-29c-3p and let-7d-5p than non-aggressive tumors (P<0.05). The findings remained significant for let-7c upon false-discovery rate correction. An excellent correlation was noticed on validation of NanoString counts by quantitative polymerase chain reaction. The comparison with published findings in adults demonstrated a unique miRNA signature in young patients with aggressive disease. Aggressive oral cavity cancer in patients <30 years old is associated with a distinctive expression pattern of the let-7 family. Larger studies including direct comparison with older patients are warranted.