Immunoexpression of lactoferrin in bone metastases and corresponding primary carcinomas

Abstract

Although the immunohistochemical presence of lactoferrin (LF) in pathological neoplastic bone and cartilage samples has previously been studied, no data concerning the distribution of LF in bone metastases of cancers that have originated from different organs are available at present. Consequently, using a monoclonal antibody, we have investigated the immunohistochemical LF pattern in 50 formalin-fixed and paraffin-embedded samples of human bone metastases and their corresponding primary carcinoma tumours (breast, 8; prostate, 4; kidney, 4; lung, 3; colon-rectum, 2 and uterus, 4). Quantification of LF immunoreactivity was performed using an intensity distribution (ID) score. LF immuno staining with a variable ID score was encountered in 11/25 (44%) metastatic lesions. In particular, the LF immunoreactivity was identified with a percentage ranging from 50 to 75% of bone metastases due to prostatic, renal, uterine and colorectal carcinomas; the positivity decreased in breast carcinomas (37.5%) and was completely absent in lung cancers. No differences in the LF-ID score were observed between primary and metastatic neoplastic localisations. Additionally, no correlations were identified between LF immunoexpression and the other parameters tested, including the age and gender of patients. Regardless of the mechanism of action of LF in human malignant tumours, we identified LF immunohistochemical reproducibility at primary and metastatic sites. Therefore, we hypothesise that the presence of LF in native neoplastic carcinomatous clones is maintained in secondary bone metastatic deposits.

Uterine large cell neuroendocrine carcinoma with unusual colonic metastasis

“…Consequently, we initially performed an immunohistochemical analysis with typical positive markers of the female genital tract, such as ER and PgR, since these receptors are usually considered useful to define the origin of unknown metastatic carcinoma. [14,15] However, the neoplastic proliferation in the present case was strongly positive for ER and negative for CDX2; therefore, it was in contrast to gastrointestinal NETs, characterized by a variable nuclear CDX2 and a negativity for ER and PgR. [5] According to these immunohistochemical findings, we have proposed to apply the same immunohistochemical panel to the colon specimens formerly removed in another hospital, that have confirmed our results supporting the diagnosis of primitive uterine LCNEC.…”

Immunohistochemical Investigation of Lactoferrin in Human Bone Primary and Metastatic Tumours

“…Recently, it has been documented an improvement of bone health by the use of LF, since this iron-binding protein stimulates the proliferation, differentiation and survival of osteoblast, significantly increasing the mineral apposition and bone formation [16][17]26,41]. In the corresponding pathologic neoplastic bone and cartilage samples, we have already reported some intriguing findings regarding LF immunoreactivity in small cohorts [22][23][24].…”

“…However, in human neoplastic conditions, LF has been extensively investigated in order to correlate its presence with the pattern of other functional neoplastic markers as well as to determine its possible prognostic role in tumors [25][26]. Therefore, we have thought to be of interest to report herein an immunohistochemical analysis of LF in a cohort of primary and metastatic neoplasms occurred in the bone by using a monoclonal specific antibody.…”

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

“…Patients, n n (%) been considered a potential marker for glandular or acinar differentiation, similar to its use in other malignancies (9,18,22). However, in breast cancer, the association between LF expression and clinical parameters is not well defined (24), even if it has been hypothesized that tumors with high LF expression retain a certain degree of physiological control over cell growth, which may explain a good prognosis (25).…”

“…Lactoferrin (LF), an iron binding 78-to 80-kDa glycoprotein usually present in mammalian milk, has been immunohistochemically revealed in numerous human neoplastic conditions of different sites (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)). An immunopositive LF rate with a large variability, ranging from 7.5 to 42% of cases, has previously been identified in breast carcinoma (23)(24)(25)(26)(27); however, LF was more often observed in low-grade ER/PR-positive ductal carcinomas, confirming a decrease in LF immunostaining in less differentiated and more aggressive breast carcinomas (25)(26)(27).…”