Primary epithelioid angiosarcoma of the thyroid: A case report.

Angiosarcoma of the thyroid is a rare and aggressive primary malignant tumour of the thyroid. We report the case of a 69-year-old woman who presented with a red and sore skin area at the right-anterior region of the neck. Ultrasound examination and computed tomography scan showed a non-homogeneous mass in the right thyroid lobe. Fine needle aspiration cytology was suggestive of atypical vascular proliferation and so the patient underwent right thyroid lobectomy. The specimen measured 6 × 5 × 2.5 cm, and a reddish nodule was found, including a whitish central area of maximum 4 cm in diameter. Immunohistochemistry showed CD31 and ERG positivity, while thyroglobulin, calcitonin and TTF-1 expression were negative, indicating a diagnosis of angiosarcoma.

Identification of a novel large EPCAM-MSH2 duplication, concurrently with LOHs in chromosome 20 and X, in a family with Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is associated with germline mutations in one of the mismatch repair genes or EPCAM. The majority of the causative alterations are point mutations. Large genomic rearrangements represent only 5-20%. Hypothetically, the allelic imbalance, like the loss of heterozygosity, may be another high penetrance risk factor. CASE PRESENTATION: We describe the case of a patient who developed 5 tumors during her lifetime and with a family history characterized by a high frequency of tumors associated with LS. The proband was tested for mutations and copy number alterations with a panel of hereditary cancer genes and by SNP array. She showed a 187 Kb duplication including EPCAM and the first 7 exons of MSH2, plus two loss of heterozygosity (LOHs) in chromosome 20 and one in chromosome X which include many tumor suppressor genes. CONCLUSION: We found a novel large EPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility. Our results underline the importance to deepen the knowledge of molecular mechanisms in order to determine the role in cancer predisposition of novel genetic alterations.

Are fine-needle aspiration biopsy-derived cell blocks a useful surrogate for tissue samples in breast cancer?

AIMS: The diagnosis of breast cancer (BC) is based on clinical examination in combination with imaging, and confirmed by pathological assessment of core needle biopsy or fine-needle aspiration biopsy (FNAB). The biological profile of the lesion is needed to define the prognosis and establish therapy. Given the importance of an early and minimally invasive diagnosis, we aimed to verify whether the biological features detected in FNAB-derived cytological material reflect the biological characteristics of surgical samples. METHODS AND RESULTS: We used immunohistochemistry and fluorescence in-situ hybridisation to study a panel of conventional biomarkers [oestrogen receptor (ER), progesterone receptor (PgR), Ki67, and human epidermal growth factor receptor 2 (HER2)] in FNAB-derived cytological samples included in cell blocks of 93 BC patients, and compared the results with those obtained from histological evaluation of the same parameters in surgical samples. Median immunopositive values of ER, PgR and Ki67 were similar in cell blocks and surgical samples. The concordance rates of ER and PgR between FNAB-derived cell blocks and histological samples were 98% and 84%, respectively. The concordance rates of Ki67 and HER2 between the two sample types were 90% and 96%, respectively. Tumour subtype classification for triple-negative and HER2-positive BCs in FNAB-derived cell blocks was always concordant with the subtype determined in surgical material. CONCLUSIONS: We demonstrated that biological marker determination in FNAB-derived cell blocks is feasible, and provides useful information and comparable results to those obtained with histological evaluation. Given the low cost of the procedure and its minimal impact on patients, we believe that cytological samples could be used as an alternative to tissue samples for early BC biomarker evaluation.

Androgen receptor in advanced breast cancer: is it useful to predict the efficacy of anti-estrogen therapy?

BACKGROUND: Androgen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET). METHODS: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002-2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to categorize AR expression. RESULTS: Among 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20% and PgR < 10% showed a statistically significant association with PD as best response. CONCLUSIONS: AR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.

Role of Telomerase in Cervical Lesions as Prognostic Marker: A Comparison Between Immunohistochemistry and Fluorescence In Situ Hybridization.

OBJECTIVES: Amplification of human telomerase is known to be associated with cervical tumorigenesis, although its role in tumor progression of cervical lesions is still unclear. We aimed to evaluate the role of telomerase in predicting the evolution of cervical lesions. METHODS: A total of 50 tissue samples taken by biopsy or conization once or repeatedly from 17 patients with cervical lesions over a 14-year follow-up was analyzed using fluorescence in situ hybridization (FISH) for hTERC gene alterations and immunohistochemistry (IHC) for hTERT expression. The accuracy of the biomarkers was measured using the area under the curve. RESULTS: Telomerase gene amplification is highly indicative of cervical lesion evolution and seems to be a more reliable biomarker than the protein expression detected by IHC. In fact, patients with benign lesions or cervical intraepithelial lesions (CINs) showing hTERC amplification relapsed or progressed into CIN 2 and CIN 3 more frequently than those without any gene amplification. FISH and IHC assays had both 86% sensitivity on conized material and 78% and 40% specificity, respectively. CONCLUSIONS: We demonstrated that the most accurate method to evaluate telomerase alterations as prognostic markers in cervical lesions was FISH assay on hTERC gene. The best accuracy was obtained using conized materials.

Benefit from anthracyclines in relation to biological profiles in early breast cancer.

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N- or 1-3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER-, PgR-, HER2-), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17-0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10-0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER-, PgR-) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ (2) = 6.72, P = 0.009). In triple unfavorable (ER-, PgR-, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26-0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15-0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors.

Gene mutation analysis in EGFR wild type NSCLC responsive to erlotinib: are there features to guide patient selection?

Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.

Case Report: Analysis of Plasma Extracellular Vesicles in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient.

Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets. Herein, we report a case of 32-years-old patient affected with of triple negative spindle-shaped MpBC. The research of molecular targets on the primary tumor did not allow performing an effective therapeutic choice. Extracellular Vesicles (EVs) are under intense study as new potential pathophysiological markers and targets for therapeutic applications, in different tumors for their role in tumor onset, progression and aggressiveness. Here, we examined the involvement of EVs in this case, to look into the MpBC microenvironment willing to identify new potential molecular targets, pathways of aggressiveness, and markers of prognosis and therapeutic efficacy. Firstly, we characterized MpBC patient EV dimensions and surface proteins. Moreover, we analyzed the EV RNA cargo supposed to be delivered to nearby and distant recipient cells. Interestingly, we observed a dysregulation EV-contained miRNAs, which could determine an increased expression of oncogenes in the tumor microenvironment, probably enabling cancer progression. These data suggest that the characterization of miRNA cargo of EVs could be important for the identification of new markers and for the application of future new target therapies.

Prognosis of ALK-rearranged non-small-cell lung cancer patients carrying TP53 mutations.

Non-small-cell lung cancer (NSCLC) is the primary cause of cancer-related death. Gene rearrangements involving the anaplastic lymphoma kinase (ALK) tyrosine kinase identify a clinical and molecular subset of NSCLC patients, who benefit from the monotherapy with ALK tyrosine kinase inhibitors. Nonetheless, responsiveness to TKIs and prognosis of these patients are influenced by several factors, including resistance mechanisms and mutations affecting genes involved in key molecular pathways of cancer cells. In a cohort of 98 NSCLC patients with ALK gene rearrangements, we investigated the role of Tumor Protein (TP53) gene mutations in predicting patients prognosis. TP53 mutations were evaluated in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).Results: In patients with available clinical and TP53 mutation information, we found that 13 patients (20.3%) were affected by TP53 mutations. Considered together, even though showing a trend, TP53 mutations were not associated with PFS and OS. Considering the different TP53 mutations by functionality in terms of disruptive and non-disruptive mutations, we observed that TP53 non-disruptive mutations were able to predict worse OS in the overall case series. Moreover, a worse PFS was seen in the subgroup of patients with TP53 non-disruptive mutation, in first-, second-, and third line of treatment. Our results show that mutations affecting TP53 gene, especially non-disruptive mutations, are able to affect prognosis of ALK-rearranged NSCLC patients.

Case Report: Analysis of Circulating Tumor Cells in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient.

Circulating tumor cells (CTCs) are a rare population of cells found in the bloodstream and represent key players in the metastatic cascade. Their analysis has proved to provide further core information concerning the tumor. Herein, we aim at investigating CTCs isolated from a 32-year-old patient diagnosed with triple negative spindle-shaped metaplastic breast cancer (MpBC), a rare tumor poorly responsive to therapies and with a dismal prognosis. The molecular analysis performed on the primary tumor failed to underline effective actionable targets to address the therapeutic strategy. Besides the presence of round-shaped CTCs, cells with a spindle shape were present as well, and through molecular analysis, we confirmed their malignant nature. This aspect was coherent with the primary tumor histology, proving that CTCs are released regardless of their morphology. Copy number aberration (CNA) profiling and variant analysis using next-generation sequencing (NGS) showed that these cells did not harbor the alterations exhibited by the primary tumor (PIK3CA G1049A mutation, MYC copy number gain). However, despite the great heterogeneity observed, the amplification of regions involved in metastasis emerged (8q24.22-8q24.23). Our findings support the investigation of CTCs to identify alterations that could have a role in the metastatic process. To the best of our knowledge, this is the first examination of CTCs in an MpBC patient.

Spotlight on PSMA as a new theranostic biomarker for bladder cancer.

Bladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.

An initiative to assess the quality of Tanzanian cervical cancer specimens for HPV and telomerase detection.

The aim of our study was to assess the quality of Tanzanian cervical cancer specimens, evaluating telomerase alterations and human papilloma virus (HPV) infection in relation to histopathological characteristics since these biomarkers are not routinely analyzed. Thirty-two Tanzanian women with invasive cervical cancer were included in the study. Histopathological classification and all the analyses on tissue, including TERT immunohistochemistry, were performed at IRST IRCCS (Meldola, Italy). HPV typization was performed by pyrosequencing. FHACT™ was used to identify chromosomal aberrations. Nonparametric ranking statistics were used. The majority (75 %) of the cases analyzed were squamous carcinoma, while 12.5 % were adenocarcinoma. The presence of HPV infection was confirmed in 26/27 (96.3 %) cases. A high percentage of patients (88 %) were infected with HPV16 of whom 12 (44.4 %) with African type 1, and 4 (14.8 %) with African type 2. TERT expression evaluated in the entire case series showed a median H-score of 130 (range 3-270), with only one negative case. 88 % of the FISH-evaluable samples showed an amplification of the chromosomal region 3q26 (TERC) and/or 5p15, and 20q13, associated with a higher median expression of TERT (P = 0.0226). Despite pre-analytical problems in terms of sample fixation, we showed that the search for biomarkers such as HPV and telomerase is feasible in Tanzanian tissue. These markers could be important risk-stratification tools in this population.

The Expression of Programmed Death Ligand 1 and Vimentin in Resected Non-Metastatic Non-Small-Cell Lung Cancer: Interplay and Prognostic Effects.

Programmed death ligand 1 (PD-L1) is an immune checkpoint with a role in cancer-related immune evasion. It is a target for cancer immunotherapy and its expression is detected for the use of some immune checkpoint inhibitors in advanced non-small cell lung cancer patients (NSCLC). Vimentin is a key component of the epithelial-to-mesenchymal transition phenotype. Its expression has negative prognostic effects in NSCLC. In this study, we retrospectively evaluated PD-L1 and vimentin expression in tumor cells, immune infiltrate and PD-L1 positive immune infiltrate via immunohistochemistry in tissue samples from resected non-metastatic NSCLC patients. We explored the interplay between PD-L1 and vimentin expression through Spearman's correlation test. We performed univariate analysis through the Cox models for demographic and clinico-pathological variables, and also for dichotomized biomarkers, i.e., PD-L1 and vimentin in tumor cells, both with 1 and 50% cutoffs. We used Kaplan-Meier method to estimate the overall survival, comparing both vimentin and PD-L1 positive patients with all the others. We found a weak positive correlation between PD-L1 and vimentin expressions in tumor cells (r = 0.25; p = 0.001). We also observed a statistically not significant trend towards a shorter overall survival in patients with both PD-L1 and vimentin expression >1% (HR = 1.36; 95% CI: 0.96-1.93, p = 0.087). In conclusion, these findings suggest that interplay between PD-L1 and vimentin may exist in non-metastatic NSCLC patients and the positivity of both markers in tumor tissue is associated with a trend towards a worse prognosis.

The Interplay Between Programmed Death Ligand 1 and Vimentin in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: Current therapy for non-small-cell lung cancer (NSCLC) frequently includes immune checkpoint inhibitors, such as pembrolizumab, and programmed death ligand 1 (PD-L1) positivity is mandatory for its use in this setting. Vimentin plays a role in carcinogenesis through the activation of the epithelial-to-mesenchymal transition (EMT) process. Its prognostic impact in NSCLC has been investigated in numerous studies but little data are available on its relation with PD-L1 expression. PATIENTS AND METHODS: We retrospectively retrieved data on patients with advanced NSCLC consecutively enrolled in a clinical trial at our institute. PD-L1 and vimentin expression were determined by immunohistochemistry. Correlations between variables were assessed using the Spearman correlation coefficient. The Kaplan-Meier method was used to estimate overall survival (OS) and the Log-rank test was used to compare survival curves. The association between demographic, clinical and biomarker information and survival was investigated with the Cox model. RESULTS: Fifty-three patients were included in the study. A weak positive correlation was observed between the PD-L1 and vimentin (ρ=0.41, P=0.003). Patients with PD-L1 values <1% showed a slightly better OS than those with higher values (HR=2.07; 95% CI: 0.92-4.65), but the difference was not significant (P=0.080). No difference in overall survival (OS) was observed on the basis of vimentin expression (HR=1.25; 95% CI: 0.59-2.66; P=0.554). Patients harboring both vimentin and PD-L1 negative expression (<1%) showed a trend towards better survival than those with ≥1% expression (HR=2.31; 95% CI: 0.87-6.17, P=0.093). No significant associations were observed between gender, age at diagnosis, stage at diagnosis, histology, KRAS or EGFR status, radical surgery or immunotherapy and OS. CONCLUSIONS: The weak positive association between PD-L1 and vimentin suggests a potential interplay between these biomarkers. Further research is warranted to evaluate EMT and immune escape as two components of the same process.

Cell-Free DNA Variant Sequencing Using CTC-Depleted Blood for Comprehensive Liquid Biopsy Testing in Metastatic Breast Cancer.

Keup and colleagues provide liquid biopsy preliminary results by sequencing variants in circulating tumor cells (CTCs) and cell-free deoxyribonucleic acid (cfDNA) "all from one tube" format, in order to use the same blood sample under the same isolation conditions of both analytes to reach an unbiased comparability and consistency. We appreciated the attempt of the authors to improve technical procedures in liquid biopsy research area, but we wanted to raise several issues related to cfDNA detection, reporting our research experience. This is a feasibility study as the authors analyzed only one sample from a small case series at an advanced line of treatment. In the clinical practice to monitor the disease and predict the treatment response, the analysis should be done at multiple time points. We have previously demonstrated that the quantity and the integrity of the cfDNA are not useful to determine the evolution of early breast cancer (bc), maybe due to the fact that cfDNA is not strictly related to cancer but also to an inflammatory status. Given that a high content of cfDNA could reflect inflammatory processes, we decided to investigate the role of stimulator of interferon gene (STING), an important regulator of cancer cell growth and senescence, in bc tissue in relation to cfDNA. STING biomarker analyzed by immunohistochemistry on tumor tissue could reflect a circulating inflammatory status and needs to be further investigated, not only on CTCs but also on cfDNA. One of the major issues of cfDNA is to decide what to analyze on it, in terms of type of cells and genetic alterations. Considering that multiple tests could be done to study gene copy number alterations, mutations, and variant fusions, the proper molecular test should be chosen, on the basis of the clinical need, starting from the treatment choice to disease monitoring.

Tumor-Infiltrating Lymphocytes (TILs) and Risk of a Second Breast Event After a Ductal Carcinoma in situ.

Women with a diagnosis of ductal carcinoma in situ (DCIS) have a high risk of developing a second breast event (SBE). The immune system might play a role in trying to prevent a SBE. Patients diagnosed with DCIS were identified in the population-based cancer registry of Area Vasta Romagna from 1997 to 2010. Median follow-up is 8.5 years. Tumor-infiltrating lymphocytes (TILs) were evaluated both in index DCIS and in SBE. The main endpoint was to assess the association between TILs' levels in index DCIS and risk of a SBE. Out of 496 DCIS patients, 100 SBEs (20.2%) were identified: 55 ipsilateral (11.1%) and 43 contralateral (8.7%). The distribution of TILs was heterogeneous, but significantly associated with grade, necrosis, screen detection and type of surgery. Patients stratified according to TILs percentage (≤5% and >5%) did not show a statistically significant difference in the 5-year cumulative incidence of SBEs: 14.9% (95% CI 11.3-19.1) and 11.0% (95% CI, 6.9-16.2), respectively (p = 0.147). In the subgroup of patients who did not receive radiotherapy, TILs >5% were associated with a reduced risk of SBE (HR 0.34, 95% CI 0.14-0.82, p = 0.016). Although we did not find any significant association between TILs and SBE, further studies evaluating their role according to radiotherapy are warranted.

Impressive clinical response to anti-PD-1 therapy in epithelioid mesothelioma with high clonal PD-L1 expression and EML4-ALK rearrangement.

OBJECTIVES: Treatment options for malignant pleural mesothelioma (MPM) are limited but some studies on immune checkpoint inhibitors (ICIs) in MPM have reported antitumor activity. Very little is known about immune-related predictive factors. MATERIALS AND METHODS: Here we report the case of a 45-year-old woman presenting with dyspnea and evidence of pleural effusion. She was diagnosed with malignant epithelioid pleural mesothelioma with brain metastasis and peritoneal carcinosis, refractory to initial standard chemotherapy treatment. Because of high PDL1 expression (100 %), she was treated with the anti-PD1 agent, pembrolizumab. RESULTS: Chemotherapy with cisplatin and pemetrexed was started, imaging studies showing stable disease after 3 treatment cycles. The patient underwent pleural decortication but rapidly progressed and thus started chemotherapy with carboplatin and gemcitabine. After 2 cycles she experienced seizures caused by a brain metastasis. This secondary lesion was surgically removed and confirmed as a metastasis from mesothelioma. Samples from both the primary tumor and the metastasis were molecularly characterized, the pleural sample proving ALK-positive and the brain sample, ALK-negative. PD-L1 was positive in 10 % of tumor cells in the pleural biopsy and 100 % in the brain lesion. Next generation sequencing analysis was negative for both samples. It was decided to start alectinib. Disease progression (peritoneal carcinosis and liver metastases) was documented after one month followed by complete bowel obstruction and recurrence in the site of the brain surgery. Alectinib was stopped and supportive care begun with parenteral nutrition via nasogastric tube. Pembrolizumab was started and after 15 days the patient's condition had significantly improved, enabling recanalization and restoration of enteral nutrition. Imaging displayed complete response of the brain metastasis, peritoneal carcinosis, bone lesions and mediastinal nodal metastases. A partial response was documented in the pleural and pulmonary nodules, with stable liver metastases. The patient is still undergoing immunotherapy and has no cancer-related symptoms. CONCLUSIONS: Our findings indicate that the use of immunotherapy in MPM warrants further investigation. Furthermore, the impressive clinical response obtained by our patient suggests that immune checkpoint inhibitors could help in the management of the disease after the failure of other treatments.

The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: a post hoc analysis of the IBIS 3 trial.

BACKGROUND: In the Italian Breast Cancer Intergroup Studies (IBIS) 3 phase III trial, we compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF) alone to sequential epirubicin/CMF regimens in patients with rapidly proliferating early breast cancer (RPEBC). We performed a post hoc analysis in the subgroup of patients with hormone-receptor-positive RPEBC on the prognostic role of progesterone receptor (PgR) status. METHODS: RPEBC was defined by thymidine labeling index (TLI) >3% or grade 3 or S-phase >10% or Ki67 >20%. We analyzed 466 patients with hormone-receptor-positive RPEBC receiving sequential epirubicin/CMF regimens followed by tamoxifen, and for whom the status of ER and PgR was available. RESULTS: Considering both cut-off values of 10% and 20%, PgR expression was significantly associated with age, menopausal status, and ER expression; HER2 status was associated with PgR status only at a cutoff value of 20% PgR. Upon univariate analysis, tumor size, nodal status, and PgR were significantly associated with disease-free survival (DFS) and overall survival (OS), while age class and local treatment type were associated only with DFS. Patients with PgR <20% showed lower 5- and 10-year DFS [hazard ratio (HR) = 1.48; 95%CI: 1.01-2.18; p = 0.044] and OS (HR = 1.85; 95%CI: 1.08-3.19, p = 0.025) rates compared with patients with PgR ⩾20%. Upon multivariate analysis, only tumor size, nodal status, and PgR were independent prognostic factors. CONCLUSIONS: Our results highlight the independent prognostic relevance of PgR expression in patients with hormone-receptor-positive RPEBC treated with adjuvant chemotherapy and endocrine therapy, where the definition of prognostic subgroups is still a major need.

Angiolipoma of the thyroid gland.

This is a report of an angiolipoma of the thyroid gland, an extremely rare entity. A thorough search of the literature revealed only one previously reported example. The patient was a 77-year-old woman with a history of a nodular lesion of the thyroid in the context of a multinodular goiter. A fine needle aspiration highlighted the presence of abundant adipocytes associated with numerous dilated vessels. Histopathologic examination of the lobectomy specimen documented the presence of a tumor composed of two main elements, namely, mature adipocytes and proliferating vessels, some of the latter containing fibrin thrombi.

Are Androgen and Estrogen Receptors in DCIS Patients Prognostic Indicators of Relapse Independently of Treatment?

Ductal carcinoma in situ (DCIS) is a highly heterogenous tumor that is now more frequently diagnosed because of the increased number of screening programs. Women with DCIS are mainly treated with conservative surgery almost always followed by radiotherapy. Although conventional biomarkers, i.e. ER, PgR, Ki67, and HER2, have been extensively investigated in invasive tumors, little is known about their role in DCIS, especially that of the androgen receptor (AR). In the present study, the expression of conventional biomarkers and AR was determined by immunohistochemistry in 85 DCIS samples from patients monitored for a maximum of 13 years: 43 patients were treated with quadrantectomy and 42 patients underwent quadrantectomy and radiotherapy. Of these, 5 and 11 patients relapsed, respectively. Our findings showed that ER and PgR were higher in nonrelapsed than in relapsed patients (P=0.025 and 0.0038). In contrast, AR expression and the AR/ER ratio were higher in relapsed patients than in the nonrelapsed group (P=0.0069 and 0.0012). At the best cut-off value of 1.1, the AR/ER ratio showed an overall accuracy of 92% and 80% in predicting in situ relapse or progression to invasive carcinoma in DCIS patients treated with surgery and those treated with surgery plus radiotherapy, respectively. AR would therefore appear to be an independent prognostic biomarker in the latter group. Our preliminary results highlight the potentially important role of the AR/ER ratio as a predictive indicator of DCIS relapse, independently of treatment.