The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.

PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma. METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed. RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001). CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

BACKGROUND: The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer. METHODS: A retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype. RESULTS: The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05). CONCLUSION: A combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.

Three Cases of Combined Therapy in Primary Breast Lymphoma (PBL) with Successful Outcomes.

Primary malignant lymphoma of the breast is a rare tumor, defined as a tumor localized in the breast with or without axillary lymph-node metastases. Such a tumor is mainly found in female patients and located more frequently in the right breast. It is difficult to make primary breast lymphoma (PBL) diagnosis before operation, and PBL diagnosis is mainly based on pathological biopsy and immunohistochemical staining. In this paper, the cases of three patients who had PBL, and who were treated for it at the Institute for Oncology and Radiology of Serbia between 2008 and 2012, are reviewed and discussed. These cases of PBL had no recorded reoccurrence of the disease and were originally treated by surgery, radiotherapy R-CHOP, and/or chemotherapy. While there is no consensus to the question of how to best treat PBL (ie, with chemotherapy, radiotherapy, or combined therapy), it is hoped that this review will offer insight into successful treatment procedures for tumors of this category.

Serum DPPIV activity and CD26 expression on lymphocytes in patients with benign or malignant breast tumors.

The aim of this work was to determine serum DPPIV activity as well as the percentage of CD26+ white blood cells and of CD26+ lymphocytes and the mean fluorescence intensity (MFI) of CD26 expression on lymphocytes in groups of patients with benign or malignant breast tumors and in healthy control people. Serum DPPIV activity was determined by colorimetric test, while CD26+ cells were counted using flow cytometer. Results of this study show that there is no statistically significant difference in serum DPPIV activity between examined groups of patients and healthy controls. However, two times higher frequency of patients with breast cancers had the enhanced DPPIV enzymatic activity in comparison to controls. Significant decrease in the percentage of CD26+ total white blood cells was found in the group of breast cancer patients and in patients with benign breast tumors compared to that found for healthy people. Although there was decrease in the percentage of lymphocytes in patients with breast tumors it was not statistically significant. The MFI of CD26 expression on these cells was significantly lower for cancer patients in comparison to healthy controls. In conclusion, this work showed the enhanced frequency of breast cancer patients with higher serum DPPIV activity. Decreased percentage of CD26+ white blood cells and decreased CD26 expression on lymphocytes are also characteristics of this group of patients. Determination of the clinical outcome of analyzed patients, 1 and 2 years after the surgical resection of the tumor, would clarify potential prognostic values of examined parameters for breast cancer.

The stage dependent changes in NK cell activity and the expression of activating and inhibitory NK cell receptors in melanoma patients.

BACKGROUND: As NK cell antitumor activity is regulated by the balance between numerous activating and inhibitory receptors the aim of this study was to analyze the changes in these receptors expression as well as the differences in their association with NK cell activity in melanoma patients in different clinical stages. MATERIALS AND METHODS: Forty-three melanoma patients in the three different clinical stages and 17 healthy controls were analyzed for NK cell activity by the standard (51)Cr radioactive assay, as well as for the percentage and absolute number of CD3-CD56+ NK cells and their subsets and the expression of degranulation marker CD107a, activating NKG2D and CD161, and inhibitory KIR, CD158a, and CD158b receptors on CD3-CD56+ NK cells by flow cytometry. IFN-γ and TNF-α PBL production were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: We show that contrary to nonmetastatic, metastatic melanoma patients have significantly impaired NK cell activity, lower CD107a expression, as well as decreased production of IFN-γ and TNF-α. Furthermore, these melanoma patients have a significant decrease in the expression of activating NKG2D receptor, which positively correlates with NK cytotoxicity, and a significant increase in the expression of inhibitory CD158b on CD3-CD56+ NK cells compared with healthy controls. CONCLUSIONS: In this study, we show that metastatic melanoma patients have significant changes in NK cell activity and the expression of activating as well as inhibitory NK cell receptors. These results indicate that only in this patient group, the blocking of inhibitory or enhancing of activating NK cell receptor expression may promote NK cell-mediated cytolysis.

Intraductal papilloma of ectopic breast tissue in axillary lymph node of a patient with a previous intraductal papilloma of ipsilateral breast: a case report and review of the literature.

The presence of ectopic breast tissue in axillary lymph nodes (ALN) is a benign condition that must be differentiated from primary or metastatic carcinoma. Here we report a patient who underwent excision of enlarged ALN 10 years after she had received surgical treatment of ipsilateral breast for an intracystic intraductal papilloma (IDP). Histological examination of the removed ALN revealed that the proliferative lesion consisted of papillary and tubular structures lined by luminal cuboidal cells and a distinct outer layer of myoepithelial cells resembling IDP of the breast. Immunostaining with a set of immunohistochemical markers including AE/AE3, alpha-smooth muscle actin and p63 in combination with estrogen and progesterone receptors confirmed the diagnosis of ectopic IDP.This case shows that even though benign proliferative change in ectopic breast tissue is an extremely rare phenomenon, this possibility should be taken into account for correct diagnosis.

Activity of MMP-2 and MMP-9 in sera of breast cancer patients.

Gelatinase A (MMP-2) and gelatinase B (MMP-9) are proteolytic enzymes involved in the process of tumor invasion, and they are considered as possible tumor markers in breast cancer patients. In this study, we examined serum activity of proMMP-2 and proMMP-9 in relation to TNM stage, tumor size, lymph node involvement, grade of differentiation of tumors, as well as steroid and Her2/neu receptor status in breast cancer patients. The activity of gelatinase in the sera of 52 patients was analyzed by SDS-PAGE zymography. The activity of proMMP-2 and proMMP-9 significantly increased with each advancing clinical stage of disease (p=0.02-0.0009) and compared to controls (p=0.015 to p<0.01). We found a positive correlation between the activity of proMMP-2 and proMMP-9 and tumor size (p=0.007; p=0.05). Patients with lymph node-positive cancer have higher proMMP-2 and proMMP-9 activity than those with node-negative cancer. ProMMP-2 and proMMP-9 activity is not associated with the expression of Her2/neu receptors, but patients with Her2/neu overexpression (3+) showed increased proMMP-2 activity. Steroid receptor score is not associated with enhanced gelatinase activity. The relationship between the increase in proMMP-2 and proMMP-9 activity in serum and tumor size and lymph node status suggests the usefulness of these enzymes as staging markers of breast cancer patients.

Effects of humoral immunity and calreticulin overexpression on postoperative course in breast cancer.

The aim was to investigate whether the humoral immunity and overexpression of calreticulin in tumor tissue determined before surgery, correlate with incidence of metastases in breast cancer patients within two years after operation. Before operation, their humoral immunity and overexpression of caleticulin and Her-2/neu in tumor tissue were analyzed by immunohystochemistry. In 23 patients with metastases in regionally lymph nodes, seven had Her-2/neu overexpression. Among those seven patients, three developed distant metastasis (two women one year and in one woman two years after surgery) and all of them showed the presence of stromal IgG immunoreactivity and overexpression of calreticulin in their tumors tissue. Preliminary data showed that serum IgG immunoreactivity to tumor stroma in combination with overexpression of calreticulin in tumor cells correlate with postoperative appearance of metastases, particularly in the group of patients with Her-2/neu overexpressed tumors and metastases in axillary lymph nodes.

Sentinel lymph node biopsy may be used to support the decision to perform modified radical neck dissection in differentiated thyroid carcinoma.

BACKGROUND: The prognostic significance of lymph node metastases (LNM) in follicle cell-derived differentiated thyroid carcinoma (DTC) is still controversial. The management of cervical lymph nodes varies from "berry picking" to modified radical neck dissection (MRND). The incidence of LNM in papillary thyroid carcinoma varies from 27% to 80%. The importance of sentinel lymph node (SLN) biopsy for decisions about the surgical management of lymph nodes in DTC has been the subject of several previous studies. PATIENTS AND METHODS: In 40 patients with DTC methylene blue dye was applied peritumorally. Both SLN and non-SLN in the lower third of the jugulo-carotid chain were dissected prior to total thyroidectomy and routine dissection of the central neck compartment and examined by frozen-section and standard histology. MRND was performed in 9 cases of LNM in the lateral neck compartment. RESULTS: The SLN identification rate was 92.5%. Metastases in SLNs were revealed by frozen-section histology in 7 cases, leading to immediate MRND. The findings were confirmed on standard HE examination. In 2 false-negative cases SLN metastases were revealed on standard histology and MRND was performed 1 week later. The specificity of the method was 100%, sensitivity 77.7%, negative predictive value 94%, positive predictive value 100%, with overall accuracy of 95%. CONCLUSION: Our results seem to imply that SLN biopsy in the jugulo-carotid chain using methylene blue dye mapping may be a feasible and valuable method for estimating lymph node status in the lateral neck compartment. It may be helpful in the detection of true-positive but nonpalpable lymph nodes, and in such cases may support the decision to perform MRND in patients with DTC.