Silver Frederick H, Kelkar Nikita, Deshmukh Tanmay, Ritter Kelly, Ryan Nicole, Nadiminti Hari
Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
OptoVibronex, LLC., Allentown, PA 18104, USA.
Biomolecules. 2021 Nov 17;11(11):1712. doi: 10.3390/biom11111712.
Early detection of skin cancer is of critical importance since the five-year survival rate for early detected skin malignancies is 99% but drops to 27% for cancer that has spread to distant lymph nodes and other organs. Over 2.5 million benign skin biopsies (55% of the total) are performed each year in the US at an alarming cost of USD ~2.5 B. Therefore there is an unmet need for novel non-invasive diagnostic approaches to better differentiate between cancerous and non-cancerous lesions, especially in cases when there is a legitimate doubt that a biopsy may be required. The purpose of this study is to determine whether the differences in the extracellular matrices among normal skin, actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) can be assessed non-invasively using vibrational optical coherence tomography (VOCT). VOCT is a new diagnostic technology that uses infrared light and audible sound applied transversely to tissue to measure the resonant frequencies and elastic moduli of cells, dermal collagen, blood vessels and fibrous tissue in skin and lesion stroma without physically touching the skin. Our results indicate that the cellular, vascular and fibrotic resonant frequency peaks are altered in AK, BCC and SCC compared to those peaks observed in normal skin and can serve as physical biomarkers defining the differences between benign and cancerous skin lesions. The resonant frequency is increased from a value of 50 Hz in normal skin to a value of about 80 Hz in pre- and cancerous lesions. A new vascular peak is seen at 130 Hz in cancerous lesions that may reflect the formation of new tumor blood vessels. The peak at 260 Hz is similar to that seen in the skin of a subject with Scleroderma and skin wounds that have healed. The peak at 260 Hz appears to be associated with the deposition of large amounts of stiff fibrous collagen in the stroma surrounding cancerous lesions. Based on the results of this pilot study, VOCT can be used to non-invasively identify physical biomarkers that can help differentiate between benign and cancerous skin lesions. The appearance of new stiff cellular, fragile new vessels, and stiff fibrous material based on resonant frequency peaks and changes in the extracellular matrix can be used as a fingerprint of pre- and cancerous skin lesions.
皮肤癌的早期检测至关重要，因为早期发现的皮肤恶性肿瘤的五年生存率为99%，但对于已扩散至远处淋巴结和其他器官的癌症，这一比例降至27%。在美国，每年进行超过250万例良性皮肤活检（占总数的55%），费用惊人，约为25亿美元。因此，迫切需要新的非侵入性诊断方法，以更好地区分癌性和非癌性病变，特别是在对是否需要活检存在合理疑问的情况下。本研究的目的是确定能否使用振动光学相干断层扫描（VOCT）非侵入性地评估正常皮肤、光化性角化病（AK）、基底细胞癌（BCC）和鳞状细胞癌（SCC）细胞外基质的差异。VOCT是一种新的诊断技术，它使用横向照射到组织的红外光和可听声音来测量皮肤和病变基质中细胞、真皮胶原蛋白、血管和纤维组织的共振频率和弹性模量，而无需物理接触皮肤。我们的结果表明，与正常皮肤中观察到的峰值相比，AK、BCC和SCC中的细胞、血管和纤维化共振频率峰值发生了改变，可作为定义良性和癌性皮肤病变差异的物理生物标志物。共振频率从正常皮肤中的50赫兹增加到癌前病变和癌性病变中的约80赫兹。在癌性病变中，在130赫兹处出现一个新的血管峰值，这可能反映了新肿瘤血管的形成。260赫兹处的峰值与硬皮病患者和已愈合皮肤伤口的皮肤中观察到的峰值相似。260赫兹处的峰值似乎与癌性病变周围基质中大量僵硬的纤维状胶原蛋白的沉积有关。基于这项初步研究的结果，VOCT可用于非侵入性地识别有助于区分良性和癌性皮肤病变的物理生物标志物。基于共振频率峰值和细胞外基质变化的新的僵硬细胞、脆弱新血管和僵硬纤维材料的出现，可作为癌前和癌性皮肤病变的指纹。
