Luana Licata

Androgen Receptor (AR), E-Cadherin, and Ki-67 as Emerging Targets and Novel Prognostic Markers in Triple-Negative Breast Cancer (TNBC) Patients

Background TNBC is an aggressive subset of breast cancer (BC) without specific target therapy. Methods This observational, retrospective study included 45 cases of TNBC. The aim of this study was to evaluate the expression of the AR, E-cadherin and Ki-67 in relation to histological type, time to relapse and overall survival (OS). Immunohistochemistry (IHC) was carried out on formalin-fixed paraffin-embedded tumor samples obtained from patients defined TNBC. Results The AR was positive (IHC >10%) in 26.6%. E-cadherin (CDH1) expression was considered positive if the score was ≥ 2. This expression was negative in 53.3% cases. The Ki-67 index was ≥ 20% in 37.7%. Univariate analyses showed that AR, CDH1 and Ki-67 are significantly associated with OS. Multivariate analysis showed that AR and Ki-67 expression are independent variables associated with OS. The statistical analysis showed that patients with AR negative and Ki-67 positive expression have a significant correlation with poor outcome. Conclusions Our data suggest that the combination of AR and E-cadherin expression as well as Ki-67 status might be useful prognostic markers in TNBC. Hence, these molecular determinants could play an interesting role to classify subgroups of TNBC.

The micropapillary/hobnail variant of papillary thyroid carcinoma: A review of series described in the literature compared to a series from one southern Italy pathology institution

Papillary thyroid carcinoma (PTC) has a good prognosis with a 10-yr survival greater than 90%. Recently, a micro-papillary pattern with hobnail appearance (MPHC) in PTC has been indicated as associated with poor prognosis, but this suggestion is based only on a few cases from geographical areas different from ours. Two-hundred ninety-nine consecutive PTC cases were collected between the years of 1992 and 2014 at our institution. The corresponding histologic sections (at least 6 for each case) were stained with hematoxylin and eosin and reviewed independently by two pathologists to reach a consensus on the identification and quantification of the MPHC. As done in other cohorts, parallel serial sections were stained with antisera for thyroglobulin, epithelial membrane antigen, thyroid-transcription-factor-1 and Ki 67. BRAF gene mutation at codon 600 and RET/PTC1 gene rearrangements were searched. A comparative statistical analysis was done between the present series and previously published series. Of the 295 PTC, 124 (42.5%) were follicular, 104 (35%) classic, 34 (11.5%) sclerosing, 15 (5%) tall cells, 10 (3.4%) Warthin-like, and 8 (2.7%) MPHC. Four MHPC cases (50%) harbored the BRAF V600E variant, while one was positive for RET/PTC1 rearrangement. Our rate of MPHC-PTC (2.7%) is 2X to 8X greater than those reported previously for cohorts from North America + North Italy, Korea and Mexico. MPHC prognosis appears to be better compared to other cohorts, probably due to not only to the lower rate of the vascular invasion, but also to the smaller size of the MPHC-PTC nodule.

HOXB13 as an immunohistochemical marker of prostatic origin in metastatic tumors.

HOBX13 is a transcription factor expressed in the normal prostatic glands and overexpressed in prostate cancer. Recent studies suggested that HOXB13 represents a prostate‐specific marker in the differential diagnosis between prostatic and urothelial carcinoma. The aim of this study was to analyze and compare the diagnostic value of HOXB13 and prostate‐specific antigen (PSA) immunoexpression for the detection of prostatic origin in metastatic tumours. PSA and HOXB13 immunohistochemical expression was assessed in 50 metastatic tumors, including 15 metastases from prostatic adenocarcinoma, 11 from lung adenocarcinoma, 12 from urinary bladder urothelial carcinoma, 11 from colorectal carcinoma, and in 1 from hepatocellular carcinoma. Strong staining for HOXB13 was observed in >75% of neoplastic cells in 15/15 (100%) metastases from prostate cancer. Weak staining in <25% of cells was found in 2/12 (17%) metastases from urothelial carcinoma. PSA immunostaining was detected only in 8 (53%) cases of prostatic origin. The sensitivity and specificity for metastatic prostate cancer were 100% and 94% for HOXB13 and 53% and 100% for PSA. Due to its high sensitivity and specificity, HOXB13 may be included in the pool of prostate‐specific markers in metastases showing absent or weak staining for PSA before excluding prostatic derivation.

Changes in human epidermal growth factor receptor 2 status between primary breast/gastric carcinomas and synchronous metastatic lymph nodes: how can we explain them?

Aim: Previous studies demonstrated discordant expression of human epidermal growth-factor receptor 2 (HER2) between primary cancer and their recurrence/metastasis. This study further evaluated HER2 status between primary gastric and breast invasive carcinomas and paired metastatic disease to lymph nodes. Methods: This study collected formalin-fixed paraffin-embedded representative tissue blocks from 62 gastric and 65 breast primary carcinomas as well as synchronous metastatic lymph nodes (male:female = 39:88; age ranged between 44 and 95 years with mean age of 69.32 years) for immunohistochemical staining of HER2 expression (DAKO HercepTest ™ kit). If immunohistochemical HER2 score reached to 2+, HER2 amplification was then assessed using fluorescence in situ hybridization (PharmDx ™ kit DAKO). Results: The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.67% in primary gastric carcinoma and corresponding nodal metastasis, while the changes in HER2 expression were revealed in 4.61% of mammary and lymph node neoplastic samples. A high-level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was confirmed in both types of cancer; the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity, mostly appreciable in gastric cancer. Conclusion: In any case, the shift from positive to negative HER2 expression suggests that trastuzumab could be the targeted treatment choice whereas the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes.

Late recurrent cutaneous breast angiosarcoma in an elderly woman: A case report

Breast angiosarcomas are malignant tumours of the vascular endothelium that arise frequently following radiation therapy. Their clinical and radiological aspects are highly heterogeneous. The current study reports an unusual case, never previously reported, of a late recurrent breast angiosarcoma occurring in an 83-year old female patient 11 years after a breast-conserving surgery followed by radiation therapy for an invasive ductal carcinoma, and 5 years after her initial angiosarcoma excision. The first physician to examine the patient noted a palpable mass near the scar and, following ultrasonography, described the breast lesion as suggestive of an abscess, despite the previous history of neoplasia. Typically, recurrences of breast angiosarcoma occur within the first postsurgical year. The present patient remains alive at 25 months after her last surgical treatment, and no evidence of any local or distant disease is observable.

Immunoexpression of lactoferrin in triple-negative breast cancer patients: A proposal to select a less aggressive subgroup

Triple-negative breast cancer (TNBC) indicates a subset of breast carcinomas that does not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). According to the literature, TNBCs are aggressive tumors, characterized by a high incidence of recurrence and a high risk of disease progression. Lactoferrin (LF) is a single-chain, iron-binding glycoprotein of ~700 amino acids, which is involved in a wide range of biological activities, including iron-trafficking and carcinogenesis. The present study aimed to assess LF expression in human TNBC samples and the possible correlation with clinico-pathological parameters associated with biological aggressiveness. LF immunohistochemical expression was investigated in formalin-fixed, paraffin-embedded samples of human TNBC. Cases were analyzed according to an intensity distribution (ID) score, and only those showing an ID score of >2 were considered as positive for LF. LF immunostaining was encountered in 26.15% cases. A significant correlation was found between LF expression and a low Ki-67 labeling index (P=0.040), the absence of recurrence (P=0.010) and alive status (P=0.020). LF may assist in identifying a subset of TNBC with less aggressive biological behavior. The meaning of LF expression in TNBC remains unclear and is controversial. The present findings indicated that LF expression is correlated with a low growth fraction in these tumors. Thus, it is possible that the inhibition of the LF axis may be a valid therapeutic target for TNBC, and this should be confirmed by future studies.

Metastatic Merkel cell carcinoma of the face

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A 59-Year Old Female with a Retrosellar Mass

A 59-year old female referred to our hospital because of a cranial trauma following an episode of loss of consciousness. Clinical history was unremarkable expect for a headache of ten-days-duration. CT scan showed a retrosellar, rounded mass, isodense with the brain parenchyma, which measured 2.8 cm in maximum size. By MRI, the mass was likely extra-axial, showed intense and heterogeneous contrast enhancement. The mass compressed, though not infiltrated, the third ventricle (Figure 1A). CT angiography showed close anatomical relationship with posterior cerebral arteries as well as with the apex of the basilar artery. At surgery, the lesion was reddish, highly vascularized and it infiltrated the hypothalamus. Due to close anatomical relationship with vital nervous and vascular structures, the lesion was submitted to only partial surgical resection. MICROSCOPIC PATHOLOGY

Clear Cell Sarcoma Of Metatarsus.

Abstract We report a case of clear cell sarcoma in the third metatarsus of the right foot. This type of tumor is very rare and scantily reported in literature. A 42-year-old Caucasian male presented with a nodular ulcerated mass on the dorsal side of the left foot. X-rays demonstrated a nodular solid lesion which dislodged the third metatarsus. A biopsy revealed a neoplastic proliferation with a sarcoma clear cell profile; because of the aggressive nature of this type of neoplasm, we performed a trans-tibial amputation according to Bugess to achieve a better functionality for the patient. The present study underlines clinical, morphological, as well as imaging and therapeutic aspects of a rare neoplasm such as clear cell sarcoma. The location site is also quite unusual - the metatarsus of the foot. The histological and immunohistochemical data were suggestive of the diagnosis of clear cell sarcoma of metatarsus. After MRI and a bone scan, the surgical treatment suggested the extension over the forefoot and the ankle and therefore a trans-tibial amputation was made.

Further immunohistochemical findings on triple-negative breast cancer

We have read with great interest AQ3 the paper of Salman et al. (2012), which appeared in the Egyptian Journal of Pathology, concerning the morphological and immunohistochemical characteristics of triple-negative breast carcinoma (TNBC) and basal breast carcinoma. In particular, the authors stressed that triple-negative as well as basal breast carcinomas exhibited some common morphological criteria, and, therefore, a positive immunostaining for CK5/6 and/or EGFR is needed to identify the basal neoplastic phenotype.