Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review.

The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients.

[Prognostic role of vascularisation and proliferation in rectal cancer with liver metastasis]. / A vascularisatio és a proliferatio prognosztikai szerepe májmetastasist adó rectumcarcinomákban.

BACKGROUND: The present study was designed to provide an analysis of factors for angiogenesis and proliferation. MATERIAL AND METHOD: We analyzed tumor tissues from 37 rectal cancer patients with concurrent or subsequent liver metastasis underwent preoperative radiotherapy, surgery and adjuvant chemotherapy. Immunohistochemistry was used for expression of proliferation (staining with anti-Ki67: MIB-1) and for detection of microvessel density (MVD, expressed by CD34). Clinicopathological findings were compared with outcome with emphasis to IHC. RESULTS: A vascular enumeration and pN status and the time of presence of the metastases has shown prognostic role along with the factors above. Increased proliferative activity of the tumor as expressed by MIB-1 staining has no prognostic value, similarly to the localization of tumor, gender, age or grading. SUMMARY: Different prognostic and predictive factors in colorectal cancer have been reported. Higher pN status and tumor vascularisation has been linked to poor prognosis in overall survival and tumor recurrence.

High levels of acute phase proteins and soluble 70 kDa heat shock proteins are independent and additive risk factors for mortality in colorectal cancer.

Recently, we reported that high soluble Hsp70 (sHsp70) level was a significant predictor of mortality during an almost 3-year-long follow-up period in patients with colorectal cancer. This association was the strongest in the group of <70-year-old female patients as well as in those who were in a less advanced stage of the disease at baseline. According to these observations, measurement of the serum level of sHsp70 is a useful, stage-independent prognostic marker in colorectal cancer, especially in patients without distant metastasis. Since many literature data indicated that measurement of C-reactive protein (CRP) and other acute phase proteins (APPs) may also be suitable for predicting the mortality of patients with colorectal cancer, it seemed reasonable to study whether the effect of sHsp70 and other APPs are related or independent. In order to answer this question, we measured the concentrations of CRP as well as of other complement-related APPs (C1 inhibitor, C3, and C9) along with that of the MASP-2 complement component in the sera of 175 patients with colorectal cancer and known levels of sHsp70, which have been used in our previous study. High (above median) levels of CRP, C1 esterase inhibitor (C1-INH), and sHsp70 were found to be independently associated with poor patient survival, whereas no such association was observed with the other proteins tested. According to the adjusted Cox proportional hazards analysis, the additive effect of high sHsp70, CRP, and C1-INH levels on the survival of patients exceeded that of high sHsp70 alone, with a hazard ratio (HR) of 2.83 (1.13-70.9). In some subgroups of patients, such as in females [HR 4.80 (1.07-21.60)] or in ≤70-year-old patients [HR 11.53 (2.78-47.70)], even greater differences were obtained. These findings indicate that the clinical mortality-prediction value of combined measurements of sHsp70, CRP, and C1-INH with inexpensive methods can be very high, especially in specific subgroups of patients with colorectal cancer.

Serum level of soluble 70-kD heat shock protein is associated with high mortality in patients with colorectal cancer without distant metastasis.

Many findings indicate that measuring the serum concentration of soluble 70-kD heat shock protein (soluble HSP70) may provide important information in cardiovascular, inflammatory, and pregnancy-related diseases; however, only scarce data are available in cancer. Therefore, using a commercial ELISA kit, we measured soluble HSP70 concentration in the sera of 179 patients with colorectal cancer. We investigated the relationship between soluble HSP70 concentration and mortality, during 33.0 (24.4-44.0) months long follow-up. High (>1.65 pg/ml, median concentration) soluble HSP70 level was a significant (hazard ratio: 1.88 (1.20-2.96, p = 0.005) predictor of mortality during the follow-up period. When we compared the soluble HSP70 levels in patients with non-resected primary tumors as compared to those who were recruited into the study 4-6 weeks after the tumor resection they were found to be significantly (p = 0.020) higher in the former group. Since the patients with non-resected primary tumors had also distant metastasis and died early, we limited the further analysis to 142 patients with no distant metastasis at the beginning of the follow-up. This association remained significant even after multiple Cox-regression analysis had been performed to adjust the data for age and sex (p = 0.028); age, sex, and TNM-T stage (p = 0.041); age, sex, and TNM-N stage (p = 0.021); age, sex, and histological grade (p = 0.023); or age, sex, and tumor localization (p = 0.029). Further analysis showed that the significant association between high HSP70 levels and poor survival is in the strongest in the group of <70-year-old female patients (HR: 5.52 (2.02-15.15), p = 0.001), as well as in those who were in a less advanced stage of the disease at baseline. These novel findings indicate that the serum level of soluble HSP70 might prove a useful, stage-independent prognostic marker in colorectal cancer without distant metastasis.

The 8.1 ancestral MHC haplotype is strongly associated with colorectal cancer risk.

Many recent data indicate that some alleles encoded in the central major histocompatibility complex (MHC) region (Class III) of short arm of chromosome 6 may modify the risk of cancer development. Therefore we determined 4 single nucleotide polymorphisms (SNPs) of this region (TNF-alpha -308 G > A, RAGE -429 T > C, HSP70-2 -1267 A > G, LTA 252 A > G) in genomic DNA samples from 183 Hungarian patients with colorectal cancer and 141 age matched control subjects representing the Hungarian population of the same age and gender. No significant differences were found in either SNP tested. When, however, three- or four-locus haplotypes consisting of known constituents of the so-called 8.1 ancestral haplotype (8.1AH) were considered, marked differences were observed. Frequency of TNF-alpha -308A, RAGE -429C, HSP70-2 -1267G, LTA 252G (8.1AH) haplotype was significantly (p = 0.006) more frequent (19.1%) among patients than in the controls (7.7%). Age- and gender-adjusted ratio of the 8.1AH carriers vs. non-carriers to have colorectal cancer was 2.514 (1.130-5.594). This risk was higher in