Immunohistochemical signaling pathways of triple negative and triple positive breast cancers: What is new?

BACKGROUND: Breast cancer (BC) is a heterogeneous disease with different clinically heterogeneous phenotypes. Triple negative BC (TNBC) (ER-/PR-/HER2-) and triple positive BC (TPBC) (ER+/PR+/HER2+) are characterized by unique clinical behavior and therapeutic challenges. However, their exact molecular pathogenesis is not well studied. This study aims to evaluate the immunohistochemical expression of androgen receptor (AR) and c-Myc in TPBCs and TNBCs, correlate their expression with the clinicopathologic features, and assess the correlation between AR and c-Myc expression in TPBCs and TNBCs. MATERIAL AND METHODS: AR and c-Myc were immunohistochemically assessed in 45 TNBC and 15 TPBC specimens. RESULTS: AR expression was detected in 17.7% of TNBC and in all TPBC specimens. c-Myc was expressed in 46.7% of TNBC and in all TPBC specimens. AR and c-Myc expression in TNBC was not associated with any of the clinicopathological features. In TPBC, AR expression was higher in older age, larger size, higher stage, and lymph node metastasis while c-Myc expression was higher in tumors with perineural invasion. This is the first study that reported a significant positive correlation between AR and c-Myc expression in TNBC and TPBC. CONCLUSION: The current results suggested that AR and c-Myc proteins may contribute to the pathogenesis of TNBC and TPBC. The positive correlation between the two proteins in these subtypes sheds new light on a distinct pathway by which BC cells can modulate their proliferation. Targeting both molecules may provide new therapeutic approaches to improve therapeutic sensitivity and patients' outcomes of these subtypes.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

BACKGROUND: The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. AIMS: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. MATERIALS AND METHODS: Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). RESULTS: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). CONCLUSIONS: The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.

Clinicopathological features of melanocytic skin lesions in Egypt.

Although melanocytic skin lesions have been recognized since antiquity, their literature was limited to Caucasians. To date, the clinicopathologic features of these lesions in Egyptians are still unknown. To define these features, diagnostic records of the melanocytic skin lesions received at the Pathology Department, Assuit University Hospitals (1989-2004) were reviewed. The lesions examined included 12 benign naevi (BN), 10 dysplastic naevi (DN), and 21 cutaneous malignant melanomas (CMMs). The DN and CMMs were more common in men than in women (2 : 1 and 1.5 : 1, respectively) while BN were more common in women (2 : 1). The average age incidence was 33+/-5, 38+/-7 and 54+/-3 years, for BN, DN and CMM, respectively. The lower limb (13/21, 62%), head and neck (7/21, 33%) were the most common sites for CMMs. The average size (mm) was 2+/-0.3, 4+/-0.6 and 21+/-0.3 for BN, DN and CMMs, respectively. Recurrence occurred in 10% of CMMs. Histologically, CMMs were of nodular type and composed of epithelioid (7/21, 33%), spindle cells (1/21, 5%), or mixed cells (13/21, 62%). The mean tumour thickness (Breslow) was 6+/-0.5 mm. CMMs included two of 21(9%), three of 21(14%), six of 21(38%), and 10 of 21(38%) with Clark level II, III, IV and V. In Egypt, CMM is the third most common cutaneous neoplasm following squamous and basal cell carcinomas. Compared with Western societies, melanoma has a male sex predilection, similar histological features but different topographical distribution and rare incidence. The striking difference from Western series is the incidence of nodular melanoma - in the West this represents 15-30% of melanomas, with superficial spreading being the majority. Another key difference from the West is the 'sun-bed' culture of the West and the desire to have suntans. This is the first study that reports the clinicopathologic features of melanocytic skin lesions in Egypt.