Afrodite Nonni

Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions

BackgroundHsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).MethodsTissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC.ResultsHsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearmans rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC.ConclusionThe above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs.

A rare case of a 39 year old male with a parasite called Dioctophyma renale mimicking renal cancer at the computed tomography of the right kidney. A case report

We present a very rare case of a 39 year old patient with Dioctophyma renale depicted as a Bosniak cyst IV of the right kidney who was finally subjected to a robotic assisted radical nephrectomy.

Heat shock protein90 in lobular neoplasia of the breast.

BackgroundHeat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast.MethodsTissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.ResultsHsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage.ConclusionHsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.

Decreased Hsp90 expression in infiltrative lobular carcinoma: an immunohistochemical study

BackgroundElevated Hsp90 expression has been documented in breast ductal carcinomas, whereas decreased Hsp90 expression has been reported in precursor lobular lesions. This study aims to assess Hsp90 expression in infiltrative lobular carcinomas of the breast.MethodsTissue specimens were taken from 32 patients with infiltrative lobular carcinoma. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment: i) the percentage of positive cells and ii) the intensity were separately analyzed. Subsequently, the Allred score was adopted and calculated. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.ResultsAll infiltrative lobular carcinoma foci mainly presented with a positive cytoplasmic immunoreaction for Hsp90. Compared to the adjacent normal ducts and lobules, infiltrative lobular carcinoma exhibited a statistically significant decrease in Hsp90 expression, both in terms of Hsp90 positive cells (%) and Allred score (74.2 ± 11.2 vs. 59.1 ± 14.2 p = 0.0001; 7.00 ± 0.95 vs. 6.22 ± 1.01, p = 0.007, Wilcoxon matched-pairs signed-ranks test). Concerning the intensity of Hsp90 immunostaining only a marginal decrease was noted (2.16 ± 0.68 vs. 1.84 ± 0.63, p = 0.087, Wilcoxon matched-pairs signed-ranks test).ConclusionILC lesions seem to exhibit decreased Hsp90 expression, a finding contrary to what might have been expected, given that high Hsp90 expression is a trait of invasive ductal carcinomas.

Synchronous Bilateral Testicular Tumors with Different Histopathology.

A 40-year-old male presented to our outpatient department with the chief complaint of a painless mass on his right testis with gradual size increase over the past two months. Physical examination and ultrasound revealed a firm and nontender mass both on the right and on the left testis. The only elevated biomarker was b-hcG (24,7 mIU/mL) and computer tomography (CT) did not reveal any pathology. Bilateral high orchiectomies were performed, without previous frozen storage of the sperm. Histology proved typical seminoma of the left testis and embryonal carcinoma of the right testis. He received two cycles of adjuvant combination chemotherapy with bleomycin, etoposide, and cisplatin. Six months after the operation no residual tumor or recurrence was observed.

Lesions of “Uncertain Malignant Potential” Diagnosed by Vacuum-Assisted Breast Biopsy: An Unclear Management?

Dear Editor, The malignancy rate of breast lesions categorized as lesions of ‘‘uncertain malignant potential’’ (B3, according to the UK breast screening program) after excision is crucial in terms of optimal management in daily clinical practice. Dillon et al. have provided an important insight into the topic in a comprehensive study based on a large number of patients and the entire spectrum of B3 and B4 lesions. However, they mainly conducted their study based on automated rather than vacuumassisted biopsy (VABB) devices, as the latter have only recently been introduced into practice. Our research team estimated the malignancy rate of B3 lesions diagnosed by VABB (11G). Independently, our research team has evaluated putative ways of minimizing underestimation rate in preinvasive breast lesions. This letter summarizes our results on B3 lesions and compares them with the results of Dillon et al. In our sample more cores were excised than internationally recommended, ranging from 24 to 96. Cases where two or more lesions coexisted were classified as a higher relative risk. A total of 131 patients with B3 lesions were diagnosed in a 3-year period; in 11 lesions the predominant diagnosis was that of radial scars, in 47 lesions papilloma, in 33 lesions atypical intraductal epithelial proliferation (AIEP), in 32 lesions lobular neoplasia (LN), and in 8 lesions phyllodes tumor. In all cases, open surgery followed and a postoperative diagnosis was established. A second pathologist blind to the preoperative diagnosis examined the tissue removed. The overall rate of malignancy in our material was 5/131 (3.8%, 95% CI: 1.3%–8.7%): 1/47 (2.1%, 95% CI: 0.1%–11.3%) in papilloma, 2/33 (6.1%, 95% CI: 0.7%–20.2%) in AIEP, and 2/32 (6.3%, 95% CI: 0.8%–20.8%) in LN; no underestimation rate was observed in radial scars (0%, one-sided, 97.5% CI: 0%–28.5%) and phyllode tumors (0%, one-sided, 97.5% CI: 0%–36.9%). The underestimation rate in our sample is lower than that reported by Dillon et al. (5/131 versus 37/177 for patients subsequently undergoing open biopsy; p\ 0.001, Pearson’s chisquare test); similarly the same p value is obtained when comparing our results to the total of the sample by Dillon et al. This discrepancy can possibly be attributed to the use of VABB device as well as to the number of cores excised during the procedure. The minimization of the underestimation rate in VABB (excising more cores) is of special interest since this observation may lead to a modified way of managing B3 lesions diagnosed by VABB. In conclusion, it can be said that our results confirm and possibly reinforce the observations of Dillon et al. viz: (1) patients with predominant RS could be monitored, (2) not all LN lesions need surgical excision, and (3) lesions with atypia are more likely to be underestimated. However, patients with a papilloma diagnosis, without other coexisting B3 lesions, could potentially be managed conservatively. Published online April 19, 2008. Address correspondence and reprint requests to: George Zografos, PhD, FACS; E-mail: gzografo@med.uoa.gr

Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status

&NA; The transcript levels of miR‐29b, which has been claimed to be involved in breast cancer molecular pathology, were evaluated with regard to their clinical utility by analyzing miR‐29b expression in 177 breast tissue samples of either benign or malignant characterization. Our data showed that miR‐29b might constitute a promising prognostic marker for invasive ductal carcinoma. Background: Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR‐29b expression in breast tumors and thus explore its clinical value. Materials and Methods: One hundred twenty‐one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real‐time polymerase chain reaction protocol was developed and miR‐29b levels, estimated via the comparative CT method, were finally subjected to comprehensive statistical analysis. Results: MiR‐29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P = .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR‐29b expression was elevated in samples with positive estrogen receptor status (P = .021) in the overall population, whereas it was negatively correlated (P = .035) with primary tumor staging in the ductal subset and increased in poorly‐differentiated tumors of lobular origin (P = .041). Furthermore, Kaplan–Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR‐29b levels had a significantly longer disease‐free survival (P = .010) and a lower risk to relapse (hazard ratio = 0.35, 95% confidence interval, 0.15‐0.81; P = .014). Conclusion: Our results provide evidence that miR‐29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.

Sampling lobular neoplasia of the breast: underestimation despite technical success?

Dear Editor, In a recently published article in Virchows Archiv, Menon et al. [1] provide interesting insight into the significance of lobular neoplasia (LN) on needle core biopsy of the breast. More specifically, commenting on 25 immediately excised LN cases, nine cases were apparently underestimated (five missed masses, two missed calcifications and two adequately sampled lesions). As a result, the overall underestimation rate is equal to nine of 25 (36%; 95%CI, 18.0–57.5%). However, as the authors noted, after the exclusion of the non-successful procedures, the underestimation rate becomes equal to two of 18 (11.1%; 95%CI, 1.4–34.7%). In this letter, we comparatively present the experience of our centre, expanding our LN series [2, 3]. Our series is based on stereotactically guided vacuum-assisted breast biopsy performed with 11 Gauge needle; indeed, the setting and needle diameter utilised may exert a significant effect upon the crucial underestimation rates. In our setting, the underestimation rate was equal to 6.1% (two of 33; 95%CI, 0.7–20.2%); interestingly enough, no cases of technical failure occurred. The underestimation rate in our setting was significantly lower than the overall underestimation rate reported by Menon et al. (two of 33 vs. nine of 25; p= 0.006, Fisher’s exact test). The above may be attributed to more accurate targeting of the lesion through the stereotactic guidance, as well as to the greater number of cores excised (24–96 cores, according to the results of a doubleblind study [3]). These two factors might effectively reduce the technical failure rate. On the other hand, our underestimation rate did not significantly differ from the one derived after the exclusion of unsuccessfully performed biopsy procedures (two of 33 vs. two of 18, p=0.607, Fisher’s exact test). That points to the existence of a lower threshold for underestimation in LN, at which different techniques and settings converge and below which needle-based techniques may not proceed. Given the small sample sizes in the various studies, imposed by the relative rarity of the LN lesion, the exact magnitude of this inherent underestimation threshold may not be accurately estimated. Indeed, this is reflected upon the large confidence intervals presented above. However, it should be noted that the underestimation rate of about 20% for LN followed by surgical excision is a well-known phenomenon, and it is partly due to the fact that LN is clinically silent and to the multicentricity of the lesion itself. To have 6% of underestimation rate is very unusual, and it might be consequent to some selection artefact [4, 5]. Virchows Arch (2009) 454:715–716 DOI 10.1007/s00428-009-0773-3